• The Korean Journal of Physiology and Pharmacology
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• v.25 no.5
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• pp.439-448
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• 2021

DA-9601 is an extract obtained from Artemisia asiatica, which has been reported to have anti-inflammatory effects on gastrointestinal lesions; however, its possible anti-inflammatory effects on the small intestine have not been studied yet. Therefore, in this study, we investigated the protective effects of DA-9601 against the ACF-induced small intestinal inflammation. Inflammation of the small intestine was confirmed by histological studies and the changes in the CD4⁺ T cell fraction induced by the inflammation-related cytokines, and the inflammatory reactions were analyzed. Multifocal discrete small necrotic ulcers with intervening normal mucosa were frequently observed after treatment with ACF. The expression of IL-6, IL-17, and TNF-α genes was increased in the ACF group; however, it was found to have been significantly decreased in the DA-9601 treated group. In addition, DA-9601 significantly decreased the levels of proinflammatory mediators such as IL-1β, GM-CSF, IFN-γ, and TNF-α; the anti-inflammatory cytokine IL-10, on the other hand, was observed to have increased. It is known that inflammatory mediators related to T cell imbalance and dysfunction continuously activate the inflammatory response, causing chronic tissue damage. The fractions of IFN-γ⁺ Th1 cells, IL-4⁺ Th2 cells, IL-9⁺ Th9 cells, IL-17⁺ Th17 cells, and Foxp3⁺ Treg cells were significantly decreased upon DA-9601 treatment. These data suggest that the inflammatory response induced by ACF is reduced by DA-9601 via lowering of the expression of genes encoding the inflammatory cytokines and the concentration of inflammatory mediators. Furthermore, DA-9601 inhibited the acute inflammatory response mediated by T cells, resulting in an improvement in ACF-induced enteritis.

• IMMUNE NETWORK
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• v.14 no.2
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• pp.89-99
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• 2014

Graft-versus-host disease (GVHD) is a fatal complication that occurs after allogeneic hematopoietic stem cell transplantation. To understand the dynamics of CD4 and CD8 T cell production of IFN-${\gamma}$ and IL-17 during GVHD progression, we established a GVHD model by transplanting T cell-depleted bone marrow (TCD-BM) and purified T cells from B6 mice into irradiated BALB.B, creating an MHC-matched but minor histocompatibility (H) antigen-mismatched transplantation (B6 ${\rightarrow}$ BALB.B GVHD). Transplantation-induced GVHD was confirmed by the presence of the appropriate compositional changes in the T cell compartments and innate immune cells in the blood and the systemic secretion of inflammatory cytokines. Using this B6 ${\rightarrow}$ BALB.B GVHD model, we showed that the production of IFN-${\gamma}$ and IL-17 by CD4 T cells preceded that by CD8 T cells in the spleen, mesenteric lymph node, liver, and lung in the BALB.B GVHD host, and Th1 differentiation predated Th17 differentiation in all organs during GVHD progression. Such changes in cytokine production were based on changes in cytokine gene expression by the T cells at different time points during GVHD development. These results demonstrate that both IFN-${\gamma}$ and IL-17 are produced by CD4 and CD8 T cells but with different kinetics during GVHD progression.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.4
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• pp.251-261
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• 2019

Allergic asthma, is a common chronic inflammatory disease of the airway presenting with airway hyperresponsiveness and airway remodelling. T helper cells-derived cytokines are critically associated with asthma pathogenesis. Janus kinase-signal transduction and activation of transcription (JAK/STAT) signaling is found to be involved in asthma. Magnolol is a plant-derived bioactive compound with several pharmacological effects. The study aimed to assess the effects of magnolol in ovalbumin (OVA)-induced asthmatic model. BALB/c mice were sensitized and challenged with OVA. Magnolol (12.5, 25, or 50 mg/kg body weight) was administered to separate groups of animals. Dexamethasone was used as the positive control. Cellular infiltration into the bronchoalveolar lavage fluid (BALF) were reduced on magnolol treatment. The levels of Th2 and Th17 cytokines were reduced with noticeably raised levels of interferon gamma. Lung function was improved effectively along with restoration of bronchial tissue architecture. OVA-specific immunoglobulin E levels in serum and BALF were decreased by magnolol. Magnolol reduced Th17 cell population and effectively modulated the JAK-STAT and Notch 1 signaling. The results suggest the promising use of magnolol in therapy for allergic asthma.

• Journal of Chest Surgery
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• v.4 no.1
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• pp.25-34
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• 1971

We observed 88 csses of primary lung cancer clinically and statistically, which had been experienced at the dept. of thoracic surgery, St. Mary's Hospital, Catholic Medical College, during the period of 7 years from January, 1964 to December, 1970. The results obtained were as follows: 1) Peak incidence of age was from 5th decade to 7th decade (86.4%), the youngest being 25 and the oldest 76. The ratio of male to female was 4.9: 1. 2) Squamous cell carcinomas showed high resectability (68.7%) and short clinical duration (188 days). Adenocarcinoma and undifferentiated carcinoma showed low resectability (33.3%, 36.4%) in spite of the more shorter clinical duration(120 days, 112 days, respectively) than squamaus cell carcinoma. 3) Positivity (above class III) in brochocopic cytology was 70.3%, and 44.8% in fresh sputum cytology. 4) Other combined pulmonary diseases (emphysema. chronic bronchitis) were noted in about one half of bronchographied 66 cases and which were considered as factors to contribute ventilatory function of lung. 5) Among 88 cases, twelve cases refused operation and 34 cases(44.7%) were operated. Seventeen cases(22.3%) out of the 34 thoracotomies were resected, 7 with lobectomy and 10 with pneumonectomy and remaining 17 cases were unresectable. 6) Histopathological findiugs of resected 17 cases were squamous cell carcinomas (11 cases), adenocarcinoll1a(1 case), undifferentiated carcinumas (4 cases) and undetermined carcinoma(l case). 7) There's no opelative mortality. Among resected 17 cases, [; cases are still alive(4 years, 3 years & 2 mo, 2 yearo, 13 mo., respectively), 7 case were expired (3 of these from remote metastasis), and remaining 5 cases were unable to follow up.

• The Korean Journal of Zoology
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• v.35 no.3
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• pp.295-307
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• 1992

In order to study the differentiation of the epithelial cells during the development of fetal rat lung tissue, histological changeB in organotypic culture and in vivo were examined. Light microscopy and scanning electron microscopy were used to analvre the histological change in rat lung from the 15th nary of gestation to the 111th nary after birth. In organotypic culture system, the pulmonary epithelial cell differentiation was studied by scanning electron microscopy. The results obtained from this study were as follows. 1. During deveiopment of lung, the glandular stage lasted from the Isth day to the lsth naut of gestation; the canalicular stage from the 17th nay to the 19th naut of gestation; the saccuiar stage from 20th nary to the birth. Alveolar stage was observed at the 3rd nary of postnatal rat lung. 2. In organotvpic culture of fetal rat lung cells organized alveolar-like structures resembling those of in uiuo state were observed on the gelatin matrix. In contrast with in vivo state, fetal lung cells formed group of type ll pneumocytes predominently along the contours of the matrix. These cells have large apical surface, short microvilli and secreted materials which may be sunactant. These results suggested that an orsanotypic culture retaining epithelial- -mesenchvmal relationships is appropriate culture model to study the pulmonary epithelial cell (especially type ll pneumocvte) differentation.

• Parasites, Hosts and Diseases
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• v.51 no.5
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• pp.583-588
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• 2013

To determine alteration of immune responses during visceral larva migrans (VLM) caused by Toxascaris leonina at several time points, we experimentally infected mice with embryonated eggs of T. leonina and measured T-helper (Th) cell-related serial cytokine production after infection. At day 5 post infection (PI), most larvae were detected from the lungs, spleen, intestine, and muscle. Expression of thymic stromal lymphopoietin (TSLP) and CCL11 (eotaxin) showed a significant increase in most infected organs, except the intestine. However, expression of the CXCL1 (Gro-${\alpha}$) gene was most highly enhanced in the intestine at day 14 PI. Th1-related cytokine secretion of splenocytes showed increases at day 28 PI, and the level showed a decrease at day 42 PI. Th2-related cytokine secretion of splenocytes also showed an increase after infection; in particular, IL-5 level showed a significant increase at day 14 PI, and the level showed a decrease at day 28 PI. However, levels of Th17-related cytokines, IL-6 and IL-17A, showed gradual increases until day 42 PI. In conclusion, Th1, Th2, and Th17-related cytokine production might be important in immune responses against T. leonina VLM in experimental mice.

• Clinical and Experimental Reproductive Medicine
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• v.44 no.4
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• pp.214-223
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• 2017

Objective: In vitro fertilization (IVF) is a well-known method for the treatment of infertility. The present study aimed to compare the differences between infertile women with successful and unsuccessful IVF outcomes regarding the expression of T helper (Th) cell transcription factors and a group of related cytokines before and after exposure to their husbands' seminal plasma. Methods: This study was performed on 19 couples with unexplained infertility undergoing IVF treatment. Among the studied group, nine and 10 couples had successful and unsuccessful IVF outcomes, respectively. This study was carried out using real-time polymerase chain reaction. Results: Before seminal plasma exposure, the expression levels of T-bet (p< 0.007), $interferon-{\gamma}$ (p= 0.013), and tumor necrosis factor $(TNF)-{\alpha}$ (p= 0.017) were higher in the infertile women with IVF failure than in those with successful IVF outcomes, while those of GATA3 (p< 0.001), Foxp3 (p= 0.001), and interleukin (IL)-35 (p< 0.003) were lower. After seminal exposure, the expression of T-bet (p= 0.02), Rorc (p< 0.001), $TNF-{\alpha}$ (p= 0.001), Foxp3 (p= 0.02), and $interferon-{\gamma}$ (p= 0.001) increased in the unsuccessful IVF group, while the expression of Foxp3 (p= 0.02), Rorc (p< 0.001), IL-23 (p= 0.04), IL-17 (p= 0.02), IL-6 (p< 0.001), transforming growth $factor-{\beta}$ (p= 0.01), and IL-35 (p< 0.001) increased in the successful IVF group. Conclusion: In summary, IVF failure was associated with imbalanced Th1/Th2/Th17/Treg responses. Moreover, our results show that seminal plasma might have a positive effect on IVF outcomes via changes in peripheral blood T cell subsets.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.11 no.1
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• pp.171-186
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• 1989

This study was undertaken to investigate the effects of indomethacin on 4-nitroquinoline 1-oxide (4NQO) induced palatal carcinoma of albino rats. Sixty albino rats about 100 gms of body weight, 6 weeks old-were used classifying as 1) six albino rats of normal group received no treatment, 2) six albino rats of control group treated with propane 1, 2-diol 3 times a week, 3) twenty four albino rats of experimental group I treated with 0.5% 4NQO in propane 1, 2-diol 3 times a week, 4) twenty four albino rats of experimental group II treated with 0.5% of 4NQO in propane 1, 2-diol 3 times a week and administrated 20${\mu}g/ml$ indomethacin in drinking water ad lib. The animals of normal and control groups were sacrificed 7th, 11th, 15th, 19th, 23rd and 27th week, while those of experimental group I and II were sacrificed 7th, 9th, 11th, 13th, 15th, 17th, 19th, 21st, 23rd, 25th, 27th and 29th week after the experiment. The palatal mucosa was excised and examined grossly, light-microscopically and electron-microscopically. Following results were obtained. 1. In control group, there was no specific difference from normal tissue histopathologically. 2. In group I, hyperkeratosis mild acantosis and dyskeratosis in in 7th week, dysplasia in 11th week and severe acantosis in 19th week were observed, but squamous cell carcinoma not observed until 29th week on light-microscope. 3. In group II, hyperkeratosis, mild acantosis in 9th week, dyskeratosis and dysplasia in 21st week, severe acantosis in 27th week and squamous cell carcinoma in 29th week were observed on light-microscope. 4. In group I, widening of intercellular space in 7th week, increasing of desmosome, giant desmosome and tonofilament in cytoplasm in 9th week, severe widening of intercellular space, increasing of mitochondria and vascular degeneration in 11th week, irregular pattern of cell feature and nucleus and prominent nucleoli in 19th week, and continuity of basal lamina in 29th week were observed on electron-microscope. 5. In group II, mild widening of intercellular space in 9th week, increasing of mitochondria, vascular degeneration and tonofilament in cytoplasm in 13th week, increasing of desmosome and giant desmosome in 15th week, irregular pattern of cell surface and nucleus and prominent nucleoli, and in 21st week continuity of basal lamina were observed on electron-microscope which phenomenon occurred little later than group I. After 21st week, however, severe widening of intercellular space, vascular degeneration and continuity of basal lamina were observed as in group I.

• Journal of Microbiology and Biotechnology
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• v.17 no.10
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• pp.1738-1741
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• 2007

The first vaccine against human papillomaviruses (HPV) formulated with HPV16 L1 virus-like particles (VLPs) produced in yeast was approved by the FDA in June 2006. Nevertheless, there have been few studies of the immunogenicity in mice of VLPs. In this study, we evaluated the cell-mediated immune response to VLPs produced in Saccharomyces cerevisiae. After immunization of mice with HPV16 L1 VLPs, we measured splenocytes proliferation and the levels of IFN$_{\gamma}$, IL2, IL4, and IL5. Splenocytes proliferation was significantly increased and a mixed Th1/Th2 response was indicated. IgG subtype immunoresponses were strongly induced and IgG1 titers were higher than those of IgG2a.

• Biomolecules & Therapeutics
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• v.20 no.2
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• pp.171-176
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• 2012

HaCaT cells are the immortalized human keratinocytes and have been extensively used to study the epidermal homeostasis and its pathophysiology. T helper cells play a role in various chronic dermatological conditions and they can affect skin barrier homeostasis. To evaluate whether HaCaT cells can be used as a model cell system to study abnormal skin barrier development in various dermatologic diseases, we analyzed the gene expression profile of epidermal differentiation markers of HaCaT cells in response to major T helper (Th) cell cytokines, such as $IFN{\gamma}$, IL-4, IL-17A and IL-22. The gene transcriptional profile of cornified envelope-associated proteins, such as filaggrin, loricrin, involucrin and keratin 10 (KRT10), in HaCaT cells was generally different from that in normal human keratinocytes (NHKs). This suggests that HaCaT cells have a limitation as a model system to study the pathophysiological mechanism associated with the Th cell cytokine-dependent changes in cornified envelope-associated proteins which are essential for normal skin barrier development. In contrast, the gene transcription profile change of human ${\beta}2$-defensin (HBD2) in response to $IFN{\gamma}$, IL-4 or IL-17A in HaCaT cells was consistent with the expression pattern of NHKs. $IFN{\gamma}$ also up-regulated transglutaminase 2 (TGM2) gene transcription in both HaCaT cells and NHKs. As an alternative cell culture system for NHKs, HaCaT cells can be used to study molecular mechanisms associated with abnormal HBD2 and TGM2 expression in response to $IFN{\gamma}$, IL-4 or IL-17A.