• Journal of the Korean Institute of Traditional Landscape Architecture
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• v.40 no.1
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• pp.26-42
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• 2022

The purpose of this study is to examine and understand the area and the original outer boundaries of Hamchunwon(含春苑), which was the outer royal garden of Gyeonghuigung Palace, which existed before the site of the Russian legation. The results of the study are as follows. First, examining the 3 types of drawings prepared for securing the Russian legation's site and constructing a new building, it was confirmed that two low peaks, which appear to be the original terrain of Hamchunwon, existed in the north and south directions inside the site. According to the initial plan of the of the legation's site, it appears that the entrance of the legation building is connected to the Saemunan-ro in the northwest. However, according to the report made at the time when the Russian temporary minister Veber purchased the legation's site, it was recorded that the site already had a narrow entrance and a dirt road in place, and hence, it was connected to Saemunan-ro. This fact makes it possible to learn that the line of movement for officials and the original gate were located to the northwest of the site planned as the entrance of the legation building towards Hamchunwon. Second, the site was created by cutting the top of the high hill at the time of the construction of the legation building, and as a result, a two tiered staircase typed terrace was built. The ground on which the main building and the secretary's building, etc., were erected was made by cutting the highest peak and solidifying it flat, and a large quantity of soil was used for grading. In the case of the northern area of the main building, the traces of leveling the terrain by cutting the mountains are apparent, and an observation typed garden with a walking path and pavilion was formed by utilizing the physical environment equipped with an easy view. This may be considered as a use which is consistent with the topographical conditions of creating an outer royal garden to block the civilian views on a high terrain overlooking the palace. Third, Hamchunwon's fences were partially exposed in the photos from the 1880s through the 1890s, which demonstrate the spatial changes made around the US, UK, and the Russian legations. As a result of the photo analysis performed, Hamchunwon occupies the northern area of the Russian legation's site, and it is estimated that the north, west, and east walls of the legation resembled those of Hamchunwon. The area to the south of the Russian legation was originally a place made available for civilian houses, and it was possible to examine the circumstances of purchasing dozens of civilian houses and farmlands according to various materials. Fourth, Hamchunwon, which was formed as the outer royal garden of Gyeongdeokgung Palace of Lord Gwanghaegun, lost its sense of place as an outer royal garden when the entire building of Gyeonghuigung Palace was torn down and used as a construction members during the reconstruction of Gyeongbokgung Palace, and faded away as the site was sold to Russia around 1885. The area where Hamchunwon used to be located transformed into a core space of the Russian legation where the main building and garden were located after the construction of the new building. Hence, Hamchunwon, which was limited to the northern area of the Russian legation, does not carry the temporal and spatial context with Gyeongungung Palace and Seonwonjeon which were constructed after 1897, and it is determined that the view of Seonwonjeon as Baehoorim or Baegyeongrim is not valid.

• MISULJARYO - National Museum of Korea Art Journal
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• v.101
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• pp.12-46
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• 2022

Completed in 1467, the Thirteen-story Stone Pagoda of Wongaksa Temple is the last Buddhist pagoda erected at the center of the capital (present-day Seoul) of the Joseon Dynasty. It was commissioned by King Sejo, the final Korean king to favor Buddhism. In this paper, I aim to examine King Sejo's intentions behind celebrating the tenth anniversary of his enthronement with the construction of the thirteen-story stone pagoda in the central area of the capital and the enshrinement of sarira from Shakyamuni Buddha and the Newly Translated Sutra of Perfect Enlightenment (圓覺經). This paper provides a summary of this examination and suggests future research directions. The second chapter of the paper discusses the scriptural background for thirteen-story stone pagodas from multiple perspectives. I was the first to specify the Latter Part of the Nirvana Sutra (大般涅槃經後分) as the most direct and fundamental scripture for the erection of a thirteen-story stone pagoda. I also found that this sutra was translated in Central Java in the latter half of the seventh century and was then circulated in East Asia. Moreover, I focused on the so-called Kanishka-style stupa as the origin of thirteen-story stone pagodas and provided an overview of thirteen-story stone pagodas built around East Asia, including in Korea. In addition, by consulting Buddhist references, I prove that the thirteen stories symbolize the stages of the practice of asceticism towards enlightenment. In this regard, the number thirteen can be viewed as a special and sacred number to Buddhist devotees. The third chapter explores the Buddhist background of King Sejo's establishment of the Thirteen-story Stone Pagoda of Wongaksa Temple. I studied both the Dictionary of Sanskrit-Chinese Translation of Buddhist Terms (翻譯名義集) (which King Sejo personally purchased in China and published for the first time in Korea) and the Sutra of Perfect Enlightenment. King Sejo involved himself in the first translation of the Sutra of Perfect Enlightenment into Korean. The Dictionary of Sanskrit-Chinese Translation of Buddhist Terms was published in the fourteenth century as a type of Buddhist glossary. King Sejo is presumed to have been introduced to the Latter Part of the Nirvana Sutra, the fundamental scripture regarding thirteen-story pagodas, through the Dictionary of Sanskrit-Chinese Translation of Buddhist Terms, when he was set to erect a pagoda at Wongaksa Temple. King Sejo also enshrined the Newly Translated Sutra of Perfect Enlightenment inside the Wongaksa pagoda as a scripture representing the entire Tripitaka. This enshrined sutra appears to be the vernacular version for which King Sejo participated in the first Korean translation. Furthermore, I assert that the original text of the vernacular version is the Abridged Commentary on the Sutra of Perfect Enlightenment (圓覺經略疏) by Zongmi (宗密, 780-841), different from what has been previously believed. The final chapter of the paper elucidates the political semantics of the establishment of the Wongaksa pagoda by comparing and examining stone pagodas erected at neungsa (陵寺) or jinjeonsawon (眞殿寺院), which were types of temples built to protect the tombs of royal family members near their tombs during the early Joseon period. These stone pagodas include the Thirteen-story Pagoda of Gyeongcheonsa Temple, the Stone Pagoda of Gaegyeongsa Temple, the Stone Pagoda of Yeongyeongsa Temple, and the Multi-story Stone Pagoda of Silleuksa Temple. The comparative analysis of these stone pagodas reveals that King Sejo established the Thirteen-story Stone Pagoda at Wongaksa Temple as a political emblem to legitimize his succession to the throne. In this paper, I attempt to better understand the scriptural and political semantics of the Wongaksa pagoda as a thirteen-story pagoda. By providing a Korean case study, this attempt will contribute to the understanding of Buddhist pagoda culture that reached its peak during the late Goryeo and early Joseon periods. It also contributes to the research on thirteen-story pagodas in East Asia that originated with Kanishka stupa and were based on the Latter Part of the Nirvana Sutra.

• Asia Marketing Journal
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• v.12 no.2
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• pp.27-52
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• 2010

It is not new that today's business organizations are expected to exhibit ethical and moral management and to carry out social responsibility as a good corporate citizen. Since South Korea emerged as a newly industrialized country during the 1980s, Korean corporations have become active in carrying out their social responsibility as a good corporate citizen to society. In spite of the short history of corporate social responsibility, Korean companies have actively participated in corporate philanthropy. Corporations' significant donations to various social causes, no-lay-off policies, corporate volunteerism and green marketing are evidences of their commitment to corporate citizenship. Corporate social responsibility is now an essential management practice whereby corporation can strengthen its sustainable value creation processes by enhancing the trust assets underlying the relationships between the business and the stakeholders. Much of the conceptual work in the area of corporate social responsibility(CSR) has originated from researches conducted in the management field. Carroll(1979) proposed that corporations have four types of social responsibilities: economic, legal, ethical and philanthropic responsibility. Most past research has investigated CSR and its impact on consumers' attitudes toward the corporations and corporate performances. Although there exists a large body of literature on how consumers perceive and respond to CSR, the majority of past studies were conducted in the United States. The stability and applicability of past findings need to be tested across different national/cultural settings, especially since corporate social responsibility is a reflection of implicit conformation with the expectations and criticism that society may have toward a corporation(Matten and Moon, 2004). In this study, we explored whether people in Korea perceive CSR of Korean corporations in the same four dimensions as done in the United States and what were the measurement items tapping each of these four dimensions. In order to investigate the dimensions of CSR and the measurement items for CSR perceived by Korean people, nine focus group interviews were conducted with several stakeholder groups(two with undergraduate students, two with graduate students, three with general consumers, and two with NGO groups). Scripts from the interviews revealed that the Korean stakeholders perceived four types of CSR which are the same as those proposed by Carroll(1979). However we found CSR issues unique to Korean corporations. For example for the economic responsibility, Korean people mentioned that the corporation needed to contribute to the economic development of the country by generating corporate profits. For the legal responsibility, Koreans included the "corporation need to follow the consumer protection law." For the ethical responsibility, they considered that the corporation needed to not promote false advertisement. In addition, Koreans thought that an ethical company should do transparent management. For the philanthropic responsibility, people in Korea thought that a corporation needed to return parts of its profits to the society for the betterment of society. The 28 items were developed based on the results of the nine focus group interviews, while considering the scale developed by Maignan and Ferrell(2001). Following the procedure proposed by Churchill(1979), we started by developing an item poll consisting of 28 items and purified the initial pool of items through exploratory, confirmatory factor analyses. 176 samples were sued for this analysis. Confirmatory factor analysis was performed on the 28 items in order to verify the underlying four factor structure. Study 1 provided new measurement items for tapping the Korean CSR dimensions, which can be useful for the future studies exploring the effects of CSR on Korean consumers' attitudes toward the corporations and corporate performances. And we found the CSR scale(17 items) has good reliability, discriminant validity and nomological validity. Economic Responsibility: "XYZ company continuously improves the quality of our products", "XYZ company has a procedure in place to respond to customer complaint", "XYZ company contributes to the economic development of our country by generating profits", "XYZ company is eager to hire people". Legal Responsibility: "XYZ company's products meet legal standards", "XYZ company seeks to comply with all laws regulating hiring and employee benefits", "XYZ company honors contractual obligations to its suppliers", "XYZ company's managers try to comply with the law related to the business operation". Ethical Responsibility: "XYZ company has a comprehensive code of conduct", "XYZ company does not promote a false or misleading advertisement", "XYZ company seems to conduct a transparent business", "XYZ company does a fair business with its suppliers or sub-contractors". Philanthropic Responsibility: "XYZ company encourages partnerships with local businesses and schools", "XYZ company supports sports and cultural activities", "XYZ company gives adequate contributions to charities considering its business size", "XYZ company encourages employees to support our community". Study 2 was condusted for comprehensive validity. 655 samples were used for this anlysis. Collected samples were tested by factor analysis and Crnbach's Alpha coefficiednts and were found to be satisfactory in terms of validity and reliability. Furthermore, fitness of the measurement model was tested by using conformatory factor analysis. χ²=880.73(df=160), GFI=0.891, AGFI=0.854, NFI=0.908, NNFI=0.913, RMR=0.059, RMESA=0.070. We hope that CSR scale could greatly facilitate research on Corporate social resposibility, it is by no means the final answer.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.822-835
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• 1997

Background : There have been many in vitro evidences that interleukin-4(IL-4) might be the most important cytokine inducing IgE synthesis from B-cells, and interferon-gamma(IFN-$\gamma$) might be a main cytokine antagonizing IL-4-mediated IgE synthesis. Recently some reports demonstrated that IFN-$\gamma$ might be used as a new therapeutic modality in some allergic diseases with high serum IgE level, such as atopic dermatitis or bronchial asthma. To evaluate the in vivo effect of IFN-$\gamma$ in bronchial asthma we tried a clinical study. Methods : Fifty bronchial asthmatics(serum IgE level over 200 IU/ml) who did not respond to inhaled or systemic corticosteroid treatment, and 17 healthy nonsmoking volunteers were included in this study. The CD 23 expressions of peripheral B-cells, the IL-4 activities of peripheral T-cells, the serum soluble CD23(sCD23) levels, and the superoxide anion(${O_2}^-$) generations by peripheral PMN were compared between bronchial asthmatics and normal subjects. The IL-4 activities of peripheral T-cells were analyzed by T-cell supernatant (T-sup)-induced CD23 expression from tonsil B-cells. In bronchial asthmatics the serum IgE levels and histamine $PC_{20}$ in addition to the above parameters were also compared before and after IFN-$\gamma$ treatment. IFN-$\gamma$ was administered subcutaneously with a weekly dose of 30,000 IU per kilogram of body weight for 4 weeks. Results : The ${O_2}^-$ generations by peripheral PMNs in bronchial asthmatics were higher than normal subjects($8.23{\pm}0.94$ vs $5.00{\pm}0.68\;nmol/1{\times}10^6$ cells, P<0.05), and significantly decreased after IFN-$\gamma$ treatment compared to initial values($3.69{\pm}0.88$ vs $8.61{\pm}1.53\;nmol/1{\times}10^6$ cells, P<0.05). CD23 expression of peripheral B-cells in bronchial asthmatics was higher than normal subjects($47.47{\pm}2.96%$, vs $31.62{\pm}1.92%$, P<0.05), but showed no significant change after IFN-$\gamma$ treatment. The serum sCD23 levels in bronchial asthmatics were slightly higher than normal subjects($191.04{\pm}23.3\;U/ml$ vs $162.85{\pm}4.85\;U/ml$), and 11(64.7%) of 17 patients showed a decreasing pattern in their serum sCD23 levels after IFN-$\gamma$ treatment. However the means of serum sCD23 levels were not different before and after IFN-$\gamma$ treatment. The IL-4 activities of peripheral T-cells in bronchial asthmatics were slightly higher than normal subjects($22.48{\pm}6.81%$ vs $18.90{\pm}2.43%$), and slightly increased after IFN-$\gamma$ treatment($27.90{\pm}2.56%$). Nine(60%) of 15 patients showed a decreasing pattern in their serum IgE levels after IFN-$\gamma$ treatment. And the levels of serum IgE were significantly decreased after IFN-$\gamma$ treatment compared to initial values ($658.67{\pm}120.84\;IU/ml$ vs $1394.32{\pm}314.42\;IU/ml$, P<0.05). Ten(83.3%) of 12 patients showed an improving pattern in bronchial hyperresponsiveness after IFN-$\gamma$ treatment, and the means of histamine $PC_{20}$ were significantly increased after IFN-$\gamma$ treatment compared to initial values ($1.22{\pm}0.29mg/ml$ vs $0.69{\pm}0.17mg/ml$, P<0.05). Conclusion : Our results suggest that IFN-$\gamma$ may be useful as well as safety in the treatment of bronchial asthmatics with high serum IgE level and that in vivo effects of IFN-$\gamma$ may be different from its in vitro effects on the regulations of IgE synthesis or the respiratory burst of PMN.

• Journal of Distribution Research
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• v.17 no.5
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• pp.1-23
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• 2012

The conflict between major corporations and small and medium-sized businesses is being aggravated, the trickle down effect is not working properly, and, as the controversy surrounding the effectiveness of the business limiting system continues to swirl, the plan proposed to protect the business domain of small and medium-sized businesses, resolve polarization between these businesses and large corporations, and protect small family run stores is the suitable business type designation system for small and medium-sized businesses. The current status of carrying out this system of selecting suitable business types among small and medium-sized businesses involves receiving applications for 234 items among the suitable business types and items from small and medium-sized businesses in manufacturing, and then selecting the items of the consultative group by analyzing and investigating the actual conditions. Suitable business type designation in the service industry will involve designation with priority on business types that are experiencing social conflict. Three major classifications of the service industry, related to the livelihood of small and medium-sized businesses, will be first designated, and subsequently this will be expanded sequentially. However, there is the concern that when designated as a suitable business type or item, this will hinder the growth motive for small to medium-sized businesses, and designation all cause decrease in consumer welfare. Also it is highly likely that it will operate as a prior regulation, cause side-effects by limiting competition systematically, and also be in violation against the main regulations of the FTA system. Moreover, it is pointed out that the system does not sufficiently reflect reverse discrimination factor against large corporations. Because conflict between small to medium sized businesses and large corporations results from the expansion of corporations to the service industry, which is unrelated to their key industry, it is necessary to introduce an advanced contract method like a master franchise or local franchise system and to develop local small to medium sized businesses through a franchise system to protect these businesses and dealers. However, this method may have an effect that contributes to stronger competitiveness of small to medium sized franchise businesses by advancing their competitiveness and operational methods a step further, but also has many negative aspects. First, as revealed by the Ministry of Knowledge Economy, the franchise industry is contributing to the strengthening of competitiveness through the economy of scale by organizing existing individual proprietors and increasing the success rate of new businesses. It is also revealed to be a response measure by the government to stabilize the economy of ordinary people and is emphasized as a 'useful way' to revitalize the service industry and improve the competitiveness of individual proprietors, and has been involved in contributions to creating jobs and expanding the domestic market by providing various services to consumers. From this viewpoint, franchises fit the purpose of the suitable business type system and is not something that is against it. Second, designation as a suitable business type may decrease investment for overseas expansion, R&D, and food safety, as well negatively affect the expansion of overseas corporations that have entered the domestic market, due to the contraction and low morale of large domestic franchise corporations that have competitiveness internationally. Also because domestic franchise businesses are hard pressed to secure competitiveness with multinational overseas franchise corporations that are operating in Korea, the system may cause difficulty for domestic franchise businesses in securing international competitiveness and also may result in reverse discrimination against these overseas franchise corporations. Third, the designation of suitable business type and item can limit the opportunity of selection for consumers who have up to now used those products and can cause a negative effect that reduces consumer welfare. Also, because there is the possibility that the range of consumer selection may be reduced when a few small to medium size businesses monopolize the market, by causing reverse discrimination between these businesses, the role of determining the utility of products must be left ot the consumer not the government. Lastly, it is desirable that this is carried out with the supplementation of deficient parts in the future, because fair trade is already secured with the enforcement of the franchise trade law and the best trade standard of the Fair Trade Commission. Overlapping regulations by the suitable business type designation is an excessive restriction in the franchise industry. Now, it is necessary to establish in the domestic franchise industry an environment where a global franchise corporation, which spreads Korean culture around the world, is capable of growing, and the active support by the government is needed. Therefore, systems that do not consider the process or background of the growth of franchise businesses and harm these businesses for the sole reason of them being large corporations must be removed. The inhibition of growth to franchise enterprises may decrease the sales of franchise stores, in some cases even bankrupt them, as well as cause other problems. Therefore the suitable business type system should not hinder large corporations, and as both small dealers and small to medium size businesses both aim at improving competitiveness and combined growth, large corporations, small dealers and small to medium sized businesses, based on their mutual cooperation, should not include franchise corporations that continue business relations with them in this system.

• Tuberculosis and Respiratory Diseases
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• v.58 no.5
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• pp.498-506
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• 2005

Background : This study compared the bronchodilator efficacy and safety of tiotropium inhalation capsules ($18{\mu}g$ once daily) with a ipratropium metered dose inhaler (2 puffs of $20{\mu}g$ q.i.d.) in patients with chronic obstructive pulmonary disease (COPD). Method : After the initial screening assessment and a two-week run-in period, patients received either tiotropium $18{\mu}g$ once daily or ipratropium $40{\mu}g$ four times daily over a period of 4 weeks in a double blind, double dummy, parallel group study. The outcome measures were the lung function, the daily records of the peak expiratory flow rate (PEFR), the patients' questionnaire, and the use of concomitant salbutamol. The forced expiratory volume in one second ($FEV_1$) and the forced vital capacity (FVC) were measured 5 minutes before inhalation, and 0.5, 1, 2 and 3 hours after inhaling the study drug on days 0, 14 and 28. Result : In 16 centers, 134 patients with a mean (SD) age of 66 (7) years and a predicted $FEV_1$ of 42 (12)% were analyzed. The trough $FEV_1$ response was significantly higher in the tiotropium group than in the ipratropium group after a four-week treatment period. The weekly mean morning PEFR of the tiotropium group was consistently higher than that of the ipratropium group during the 4-week treatment period with differences ranging from 12.52 to 13.88 l/min, which were statistically significant. Tiotropium was well tolerated by the COPD patients during the 4-week treatment period and had a similar safety profile to ipratropium. Conclusion : This study shows that tiotropium administrated once daily has a superior bronchodilator effect with a similar safety profile in treating COPD patients compared with ipratropium, inhaled four times daily.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1236-1251
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• 1998

Background : TNF-$\alpha$ appears to be a central mediator of the host response to sepsis. While TNF-$\alpha$ is mainly considered a proinflammatory cytokine, it can also act as a direct cytotoxic cytokine. However, there are not so many studies about the relationship bet ween TNF-$\alpha$ level and lung injury severity in ALI, particularly regarding the case of ALI caused by direct lung injury such as diffuse pulmonary infection. Recently, a natural defense mechanism, known as the stress response or the heat shock response, has been reported in cellular or tissue injury reaction. There are a number of reports examining the protective role of pre-induced heat stress proteins on subsequent LPS-induced TNF-$\alpha$ release from monocyte or macrophage and also on subsequent LPS-induced ALI in animals. However it is not well established whether the stress protein synthesis such as HSP can be induced from rat alveolar macrophages by in vitro or in vivo LPS stimulation. Methods : We measured the level of TNF-$\alpha$, the percentage of inflammatory cells in bronchoalveolar lavage fluid, protein synthesis in alveolar macrophages isolated from rats at 1, 2, 3, 4, 6, 12, and 24 hours after intratracheal LPS instillation. We performed histologic examination and also obtained histologic lung injury index score in lungs from other rats at 1, 2, 3, 4, 6, 12, 24 h after intratracheal LPS instillation. Isolated non-stimulated macrophages were incubated for 2 h with different concentration of LPS (0, 1, 10, 100 ng/ml, 1, or 10 ${\mu}g/ml$). Other non-stimulated macrophages were exposed at $43^{\circ}C$ for 15 min, then returned to at $37^{\circ}C$ in 5% CO2-95% for 1 hour, and then incubated for 2 h with LPS (0, 1, 10, 100ng/ml, 1, or 10 ${\mu}g/ml$). Results : TNF-$\alpha$ levels began to increase significantly at 1 h, reached a peak at 3 h (P<0.0001), began to decrease at 6 h, and returned to control level at 12 h after LPS instillation. The percentage of inflammatory cells (neutrophils and alveolar macrophages) began to change significantly at 2 h, reached a peak at 6 h, began to recover but still showed significant change at 12 h, and showed insignificant change at 24 h after LPS instillation compared with the normal control. After LPS instillation, the score of histologic lung injury index reached a maximum value at 6 h and remained steady for 24 hours. 35 kDa protein band was newly synthesized in alveolar macrophage from 1 hour on for 24 hours after LPS instillation. Inducible heat stress protein 72 was not found in any alveolar macrophages obtained from rats after LPS instillation. TNF-$\alpha$ levels in supernatants of LPS-stimulated macro phages were significantly higher than those of non-stimulated macrophages(p<0.05). Following LPS stimulation, TNF-$\alpha$ levels in supernatants were significantly lower after heat treatment than in those without heat treatment (p<0.05). The inducible heat stress protein 72 was not found at any concentrations of LPS stimulation. Whereas the 35 kDa protein band was exclusively found at dose of LPS of 10 ${\mu}g/ml$. Conclusion : TNF-$\alpha$ has a direct or indirect close relationship with lung injury severity in acute lung injury or acute respiratory distress syndrome. In vivo and in vitro LPS stimulation dose not induce heat stress protein 72 in alveolar macrophages. It is likely that 35 kDa protein, synthesized by alveolar macrophage after LPS instillation, does not have a defense role in acute lung injury.

• Tuberculosis and Respiratory Diseases
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• v.49 no.6
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• pp.691-702
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• 2000

Background : Acute lung injury (ALI) is a commonly encountered respiratory disease and its prognosis is poor when the treatment is not provided promptly and properly. However no specific pharmacologic treatment is currently available for ALI, although recently several supportive drugs have been under scrutiny. We studied anti-inflammatory effects of pentoxifylline (PF), a methylated xanthine, and ONO-5046, a synthetic neutrophil elastase inhibitor on lipopolysaccharide (LPS)-induced ALI in vitro. Methods : To establish an in vitro model of LPS-induced ALI, primary rat alveolar macrophages and peripheral neutrophils in various ratios (1:0, 5:1, 1:1, 1:5, 0:1) were co-cultured with transformed rat alveolar epithelial cells (L2 cell line) or vascular endothelial cells (IP2-E4 cell line) under LPS stimulation. Each experiment was divided into five groups-control, LPS, LPS+PF, LPS+ONO, and LPS+PF+ONO. We compared LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils in various ratios, and the resultant cytotoxicity on L2 cells or IP2-E4 cells between groups. In addition we also compared the productions of tumor necrosis factor (TNF)-$\alpha$ interleukin (IL)-$1{\beta}$, monocyte chemotactic protein(MCP)-1, IL-6, and IL-10 as well as mRNA expressions of TNF-$\alpha$ inducible nitric oxide synthetase(iNOS), and MCP-1 from LPS-stimulated primary rat alveolar macrophages between groups. Results : (1) PF and ONO-5046 in each or both showed a trend to suppress LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils regardless of their ratio, except for the LPS+PF+ONO group with the 1:5 ratio, although statistical significance was limited to a few selected experimental conditions. (2) PF and ONO-5046 in each or both showed a trend to prevent IP2-E4 cells from LPS-induced cytotoxicity by primary rat alveolar macrophages and peripheral neutrophils regardless their ratio, although statistical significance was limited to a few selected experimental conditions. the effects of PF and/or ONO-5046 on LPS-induced L2 cell cytotoxicity varied according to experimental conditions. (3) PF showed a trend to inhibit LPS-induced productions of INF-$\alpha$ MCP-1, and IL-10 from primary rat alveolar macrophages. ONO-5046 alone didnot affect the LPS-induced productions of proinflammatory cytokines from primary rat alveolar macrophages but the combination of PF and ONO-5046 showed a trend to suppress LPS-induced productions of INF-$\alpha$ and IL-10 PF and ONO-5046 in each or both showed a trend to increase LPS-induced IL-$\beta$ and IL-6 productions from primary rat alveolar macrophages. (4) PF and ONO-5046 in each or both showed a trend to attenuate LPS-induced mRNA expressions of TNF-$\alpha$ and MCP-1 from primary rat alveolar macrophages but at the same time showed a trend increase iNOS mRNA expression. Conclusion : These results suggest that PF and ONO-5046 may play a role in attenuating inflammation in LPS-induced ALI and that further study is needed to use these drugs as a new supportive therapeutic strategy for ALI.

• Tuberculosis and Respiratory Diseases
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• v.56 no.1
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• pp.51-66
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• 2004

Objectives : The matrix metalloproteinases (MMPs) that participate in the extracellular matrix metabolism play a important role in the progression of pulmonary fibrosis. The effects of the MMPs are regulated by several factors including Th-1 cytokines, $interferon-{\gamma}$ ($IFN-{\gamma}$). Up to now, $IFN-{\gamma}$ is known to inhibit pulmonary fibrosis, but little is known regarding the exact effect of $IFN-{\gamma}$ on the regulation of the MMPs. This study investigated the effects of $interferon-{\gamma}$ on the pulmonary fibrosis and the expression of the lung MMP-2,-9, TIMP-1,-2, and Th-2 cytokines in aa rat model of bleomycin induced pulmonary fibrosis. Materials and methods : Male, specific pathogen-free Sprague-Dawley rats were subjected to an intratracheal bleomycin instillation. The rats were randomized to a saline control, a bleomycin treated, and a bleomycin+$IFN-{\gamma}$ treated group. The bleomycin+$IFN-{\gamma}$ treated group was subjected to an intramuscular injection of $IFN-{\gamma}$ for 14 days. At 3, 7, 14, and 28 days after the bleomycin instillation, the rats were sacrificed and the lungs were harvested. In order to evaluate the effects of the $IFN-{\gamma}$ on lung fibrosis and inflammation, the lung hydroxyproline content, inflammation and fibrosis score were measured. Western blotting, zymography and reverse zymography were performed at 3, 7, 14, 28 days after bleomycin instillation in order to evaluate the MMP-2,-9, and TIMP-1,-2 expression level. ELISA was performed to determine the IL-4 and IL-13 level in a lung homogenate. Results : 1. 7 days after bleomycin instillation, inflammatory changes were more severe in the bleomycin+$IFN-{\gamma}$ group than the bleomycin group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$2.08{\pm}0.15:2.74{\pm}0.29$, P<0.05), but 28 days after bleomycin instillation, lung fibrosis was significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$3.94{\pm}0.43:2.64{\pm}0.13$, P<0.05). 2. 28 days after bleomycin instillation, the lung hydroxyproline content was significantly reduced as a result of $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$294.04{\pm}31.73{\mu}g/g:194.92{\pm}15.51{\mu}g/g$, P<0.05). 3. Western blotting showed that the MMP-2 level was increased as a result of the bleomycin instillation and highest in the 14 days after bleomycin instillation. 4. In zymography, the active forms of MMP-2 were significantly increased as a result of the $IFN-{\gamma}$ treatment 3 days after the bleomycin instillation, bleomycin+$IFN-{\gamma}$ group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$209.63{\pm}7.60%:407.66{\pm}85.34%$, P<0.05), but 14 days after the bleomycin instillation, the active forms of MMP-2 were significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$159.36{\pm}20.93%:97.23{\pm}12.50%$, P<0.05). 5. The IL-4 levels were lower in the bleomycin and bleomycin+$IFN-{\gamma}$ groups but this was not significant, and the IL-13 levels showed no difference between the experiment groups. Conclusion : The author found that lung inflammation was increased in the early period but the pulmonary fibrosis was inhibited in the late stage as a result of $IFN-{\gamma}$. The inhibition of pulmonary fibrosis by $IFN-{\gamma}$ appeared to be associated with the inhibition of MMP-2 activation by $IFN-{\gamma}$. Further studies on the mechanism of the regulation of MMP-2 activation and the effects of MMP-2 activation on pulmonary fibrosis is warranted in the future.