• Journal of Life Science
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• v.33 no.10
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• pp.767-775
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• 2023

Sulfasalazine is a disease-modifying antirheumatic abiotic agent. It is a derivative of aminosalicylic acid and has been used for the treatment of various inflammatory diseases, such as rheumatoid arthritis, ulcerative colitis, and Crohn's disease, since it was first synthesized in 1941 and approved as a medicine in the United States in 1950. However, its mechanism of action has not yet been clearly identified. In this study, the effects of sulfasalazine on cell survival, apoptosis, and cell cycle progression in macrophages, which are major immune cells that regulate inflammatory responses, were investigated using mouse macrophage RAW 264.7 cells. Sulfasalazine inhibited the viability of RAW 264.7 cells in a dose-dependent manner, starting at a concentration of 0.25 mM. Annexin-V staining was used to confirm that the decrease in cell viability was due to apoptosis, and the number of Annexin-V-positive cells increased significantly at a concentration of 0.25 mM or higher. The effect of sulfasalazine on the expression of key proteins that regulate the G0/G1 phase of the cell cycle was also investigated. Sulfasalazine treatment significantly increased the expression of the cyclin-dependent kinase inhibitors p21 and p27 in RAW 264.7 cells. Although sulfasalazine is frequently used as a control drug in studies on inflammatory diseases, such as inflammatory colitis and rheumatoid arthritis, studies on its effect on macrophages are very limited. Therefore, the results of this study are expected to provide vital information on the use of sulfasalazine as a disease treatment.

• Tuberculosis and Respiratory Diseases
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• v.57 no.4
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• pp.336-344
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• 2004

Background : Immunotherapy for cancer has not been successful because of several obstacles in tumor and its environment. Inappropriate secretions of cytokines and growth factors by tumors cause substantial changes in the immune responses against tumors, affording the tumors some degree of protection from immune attack. Uteroglobin (UG, Clara cell secretory protein) has been known to have anti-inflammatory, immunomodulatory and anti-cancer activities. However, in lung cancer cells, UG expression is decreased. This study investigated the role of UG in the immunomodulation of lung cancer. Methods : The UG protein was overexpressed by Adenovirus(Ad)-UG transduction in non-small cell lung cancer cell lines. The concentration of Prostaglandin $E_2$ ($PGE_2$) was measured by Enzyme Immunoassay (EIA). Peripheral blood mononuclear cells (PBMC) from whole blood were prepared with Ficoll. PBMC were cultured in RPMI 1640, supernatant of A549, or A549 with UG or NS-398. Concentration of Th 1 type and Th 2 type cytokines from PBMC were measured by ELISA. Results : UG suppressed $PGE_2$, Cyclooxygenase-2 (COX-2) product. Both Th1 type such as Interleukin-2 (IL-2), Interferon-${\gamma}$ (IFN-${\gamma}$) and Tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and Th2 type cytokines such as IL-10 and Tumor growth factor-${\beta}$ (TGF-${\beta}$) were increased when PBMC were cultured with supernatant of non small lung cancer cells. UG and COX-2 inhibitor, NS-398 induced normal immune response of PBMC. Although Th 1 type cytokines were increased, Th 2 type cytokines were reduced by UG. Conclusion : UG suppressed PGE2, COX-2 product. Supernatant of NSCLC induced imbalance of immune response of PBMC. However, UG reversed this imbalance. These results suggest that UG may be used in the development of immunotherapy for lung cancer.

• Journal of Animal Science and Technology
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• v.47 no.6
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• pp.947-954
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• 2005

This study was conducted to investigate the effects of hydrolyzed Lactobacillus supplementation with digestive enzymes treatment on the macrophage activation, the induction of nitric oxide(NO), interleukin (IL)-6 and tumor necrosis factor(TNF)-$\alpha$. The RAW 264.7 murine macrophage was exposed to porcine Lactobacillus strains which were digested with both pepsin and pancreatin. The production of NO, TNF-$\alpha$ and IL-6 in the macrophage were strain and dose-dependent, respectively. The induction of NO and cytokines were higher in both 3149 and 3146 strains compared with other Lactobacillus strains. Overall, the level of NO was observed at the lower range between 10 and 150 μg hydrolysates per ml, whereas IL-6 and TNF-$\alpha$ were observed at relatively higher concentration between 50 and 300 μg hydrolysates per ml. Lactobacillus strains which produced a high level of NO also showed a high induction of TNF-$\alpha$ and IL-6. Therefore, the present results suggest that hydrolysates of Lactobacillus strains are related to induction of several macrophage mediators, and then it could be beneficially used to modulate gastrointestinal immune function of the host. Also, the methodogly employed in this study might be useful to investigate the effects of lactic acid bacteria on gastrointestinal immunity.

• Journal of Hospice and Palliative Care
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• v.20 no.3
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• pp.159-166
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• 2017

According to the advance of antiretroviral regimen and the early treatment strategy, people living with human immunodeficiency virus (PLWH) are achieving the goal of virologic suppression and immune restoration. Most of them no more die of acquired immunodeficiency syndrome (AIDS) defining illnesses, and become older with chronic comorbidities such as cardiovascular, metabolic, hepatic, renal and neurological diseases. However some PLWH still visit hospitals as late presenters with very low CD4+ T cell counts, so that they suffer AIDS defining illnesses to die or experience severe neurological complications resulting in disabilities. Early palliative interventions are needed on the various symptoms of PLWH. Thus far chronic pains such as distal symmetric sensory polyneuropathies have been underevaluated. Active pain-relieving interventions are important to them. Recently we define end of life condition of human immunodeficiency virus (HIV) or eligibility to hospice care after adjusting current status of HIV treatment. Hospice teams should pay attention to the specific medical conditions, psychological needs, and social circumstances of PLWH. With just standard precautions as common infection control measures, general hospice cares can be provided to them like to other hospices subjects. For giving PLWH opportunities to have the end of life with value and dignity, hospice multidisciplinary team should intervene them early and aggressively. Now we need more clinical experiences and institutional improvements.

• Applied Biological Chemistry
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• v.35 no.6
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• pp.462-469
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• 1992

Two kinds of complement activating (anti-complementary) polysaccharides, which were expected to be immunomodulators were purified from Arecae Pericarpium (the pericarps of Areca catechu), and their action modes have been studied. The active polysaccharides, AC-2-IIIa and AC-2-IIIc from Arecae Pericarpium showed dose-dependent anti-complementary activities on $TCH_{50}$. The anti-complementary activities of AC-2-IIIa and AC-2-IIIc in metal ion-free condition were completely decreased in comparison with control whereas in case of $Ca^{2+}$-free condition, these activities were maintained, considerably. Also AC-2-IIIa and AC-2-IIIc showed relatively potent alternative complement pathway activities. Furthermore, after incubation of the normal human serum with polysaccharide of Arecae Pericarpium in the absence of $Ca^{2+}$ ion, a cleavage of C3 in the serum was found to have occurred through immunoelectrophoresis (IEP) with anti-human C3. Also, from the results of IEP using anti-human whole serum, the ratios of the height of 3rd peak to ${\alpha}2-M$ peak by AC-2-IIIa and AC-2-IIIc proved to be $1.50{\pm}0.04$ and $1.22{\pm}0.08$, respectively. These results indicate that the modes of complement activation by AC-2-IIIa and AC-2-IIIc from Arecae Pericarpium are via both the classical pathway and the alternative pathway.

• The Journal of Pediatrics of Korean Medicine
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• v.15 no.1
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• pp.71-75
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• 2001

백혈병은 조혈계통의 악성 증식성 질환으로서 현재까지 주로 화학약물요법에 의존하고 있는 실정이다. 화학약물요법은 백혈병 세포를 소멸시킬 수 있지만 또한 인체에 여러 가지 독성 반응 및 부작용을 일으키기도 한다. 따라서 중서의결합으로 백혈병 치료에 접근하는 것은 중요한 의미를 갖는다. 중의학에서 소아 백혈병을 치료하는 경우 청열해독법(淸熱解毒法), 부정보허법(扶正補虛法), 활혈화어법(活血化瘀法)을 주로 사용한다. 청열해독법은 백혈병의 조기치료에 주로 활용되는데, 인체의 저항력을 증강시켜 화학약물요법을 실시하는 동안 흔히 나타날 수 있는 감염증상을 예방하는 효과를 얻을 수 있다. 부정보허법(扶正補虛法)은 주로 화학약물요법의 유도 완화기 및 치료효과의 유지를 위하여 활용되는데, 이는 인체의 면역력을 향상시켜 화학약물요법이 인체에 미치는 손상을 경감시킬 수 있다. 활혈화어법(活血化瘀法)은 미세순환을 개선시키는 작용을 하며 골수의 조혈기능을 촉진하고 면역기능을 조절하며 또한 일부 활혈화어제(活血化瘀劑)는 백혈병 세포에 직접적인 억제효과를 보인다. 소아백혈병에 대하여 화학약물요법을 진행하는 동안 중약을 같이 병행하는 경우 다음과 같은 과정으로 나누어 실시할 수 있다. 1. 유도완화치료(화학요법)단계: 이와 같은 치료과정은 대개 화학약물요법으로 인한 극심한 독성반응이나 주작용을 나타내게 되는데, 이 과정에서 중약치료를 병행하면 신속하게 증상을 개선시킬 수 있다. 만약 구토나 설사와 같은 소화계 부작용이 나타나면 화위강역법(和胃降逆法)을 활용하고, 감염 증상이 나타나면 부정(扶正)과 거사법(祛邪法)을 병행할 수 있다. 화학약물요법을 진행한 후 신체가 극도로 허약해지고 골수의 기능이 심하게 억제되는 경우는 주로 부정(扶正)시키는 중약을 사용하면서 익기양혈제(益氣養血劑)를 곁들이고 보조적으로 단삼(丹蔘), 당귀(當歸), 천궁(川芎), 계혈등(鷄血藤) 등과 같은 활혈화어제(活血化瘀劑)를 사용하여 골수의 조혈기능을 회복시킨다. 2. 치료효과의 유지단계: 본 과정에서는 중약치료에 있어서 부정(扶正)과 거사법(祛邪法)을 병행한다. 화학약물요법을 실시하는 동시에 거사제(祛邪劑)를 중용(重用)함으로써 화학약물요법의 효과를 강화시킨다. 화학약물요법이 끝난 뒤 부정(扶正)시키는 약물을 중용(重用)하여 인체의 면역기능을 증강시키고 백혈병세포를 억제시킨다. 3. 치료효과의 유지 및 강화단계: 치료효과의 유지단계에서는 변증논치(辨證論治)의 원칙에 입각하여 항암효과가 있는 중약을 활용할 수 있는데, 예를 들어 백화사설초(白花蛇舌草), 산자고(山慈?), 청대(靑黛), 용규(龍葵) 등을 사용할 수 있고, 육신환(六神丸)을 장기적으로 복용하여도 된다. 소아백혈병 치료에 있어서 중서의결합의 치료법을 활용하는 경우 다음과 같은 내용에 주안점을 둘 수 있다. 화학약물요법을 진행하는 과정에서 중약을 병행하여 투여하는 경우 사진합삼(四診合參)을 근간으로 종합적인 분석을 통하여 병인(病因)을 살피어 치료에 임하도록 한다. 약물의 선택과 처방의 구성은 반드시 변증논치(辨證論治)의 원칙하에 이루어져야 한다. 화학약물요법과 중약치료를 병행하는 과정에서 변증(辨證)과 변병(辨病)이 서로 결합되고 부정(扶正)과 거사법(祛邪法)을 병행하여 활용한다. 정체관(整體觀)에서 출발하여 환자를 관찰하는 동시에 특징적인 증후(證候)에 대한 변증논치(辨證論治)도 중요하며, 또한 백혈병 환자의 유형(類型)이나 임상 혈액검사 소견, 골수의 양상, 화학요법의 진행단계 및 환자의 연령과 체질 등을 충분히 가만하여 종합적인 분석을 토대로 치료법을 선택하여야 중약요법과 화학약물요법의 협동적인 효과를 증폭시키고 백혈병치료에 새로운 전기를 마련할 수 있을 것이다.

• Journal of Life Science
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• v.19 no.8
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• pp.1067-1072
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• 2009

Stromal derived factor-1 (SDF-1 or CXCL12), one of the CXC chemokines, is widely expressed in many tissues, including the thymus. The thymus can regenerate to its normal mass within 14 days after acute involution induced by cyclophosphamide (CY) in adult rats. Despite the established role of SDF-1 signaling in the development of T and B lymphocytes in the thymus, it has not yet been associated with the regeneration of the adult thymus. The purpose of this study was to investigate whether SDF-1, which is expressed in thymic stromal cells, is modulated during thymic regeneration in adult rats. Here, we showed that SDF-1 mRNAs were expressed in high levels in the thymocyte and thymic stromal cells at day 7 of the CY model. SDF-1 protein was shown to be present at the cortex-medulla junction, paraseptum and within the thymic medulla. Double-immunofluorescence for SDF-1 and ED-1 showed that strong SDF-1 expression was detected in the macrophages of the medulla region displaying immunoreactivity for ED-1 during thymus regeneration. Taken together, our results demonstrated that SDF-1 expression increased in regenerating thymic macrophages, suggesting the roles of SDF-1 as a chemo-attractant for damaged cells produced in the process of thymic regeneration after acute involution induced by CY.

• Food Engineering Progress
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• v.22 no.4
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• pp.337-343
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• 2018

Coffee is a commonly consumed beverage that contains anti-inflammatory compounds such as caffeine, chlorogenic acid, cafestol, trigonelline, and kahweol. Lactobacillus plantarum is a lactic acid bacterium most frequently used in the fermentation of food products of plant origin. L. plantarum is able to degrade some food phenolic compounds and provide high value-added compounds such as powerful antioxidants or food additives approved as flavouring agents. In this study, we investigated the anti-inflammatory effects of coffee extract fermented by L. plantarum on RAW264.7 macrophages. In lipopolysaccharide-stimulated RAW264.7 cells, these coffee extracts exhibited anti-inflammatory activities through the reduction of nitric oxide (NO) production and inducible NO synthase expression. Fermented coffee extracts significantly decreased the expression of inflammatory cytokines such as tumor necrosis factor ${\alpha}$, interleukin $1{\beta}$, interleukin 6, and interferon ${\gamma}$. Cyclooxygenase-2, which is one of the key biomarkers for inflammation, was significantly suppressed. These results might be helpful for understanding the anti-inflammatory mechanism of fermented coffee extract on immune cells and, moreover, suggest that fermented coffee extract may be a beneficial anti-inflammatory agent.

• Journal of Biomedical Engineering Research
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• v.15 no.1
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• pp.41-50
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• 1994

The chemotherapy using macromolecules, i.e., monoclonal antibodies loaded with anticancer agents hasn't been successful in delivering therapeutic amount of the conjugates. The comprehensive evaluation of mass transfer factors in tumor is prerequisite for the development of the effective chemotherapy. Characterization of neuroblastoma implanted in immunosuppressed athymic nude rats was performed. Its growth kinetics, glucose metabolic rate (GMR) were measured along with the interstitial fluid pressure (IFP), blood perfusion rate (BPR) and pH distribution throughtout the tumor radius. Volume doubling time and GMR were 8.1 days(SD 0.44 day), 23.53 mg/min/100 g(SD 3.54 mg/min/100 g), respectively. The IFP in tumor center was increased with tumor volume, and approached to 3 mmHg (SD 2.6 mmHg) when the tumor was 3 cm high. The radial distribution of IFP, BPR and pH in 2 cm high tumors showed that BPR and pH were decreased, while IFP was increased as the ~ensors moved toward the tumor center. The elevated IFP, decreased BPR and pH in tumor center suggested that the delivery of conjugates might be increased by properly manipulating mass transfer factors.

• Korean Journal of Clinical Laboratory Science
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• v.55 no.4
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• pp.306-313
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• 2023

Sepsis is a systemic inflammatory response, with manifestations in multiple organs by pathogenic infection. Currently, there are no promising therapeutic strategies. Signal transducer and activator of transcription 3 (STAT3) is a cell signaling transcription factor. Niclosamide is an anti-helminthic drug approved by the Food and Drug Administration (FDA) as a potential STAT3 inhibitor. C57BL/6 mice were treated with an intraperitoneal injection of lipopolysaccharide (LPS). Niclosamide was administered orally 2 hours after the LPS injection. This study found that Niclosamide improved the survival and lung injury of LPS-induced mice. Niclosamide decreased the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) in serum. The effects of Niclosamide on phosphoinositide 3-kinase (PI3K), AKT, nuclear factor-κB (NF-κB), and STAT3 signaling pathways were determined in the lung tissue by immunoblot analysis. Niclosamide reduced phosphorylation of PI3K, AKT, NF-κB, and STAT3 significantly. Furthermore, it reduced the phosphorylation of STAT3 by LPS stimulation in RAW 264.7 macrophages. Niclosamide also reduced the LPS-stimulated expression of proinflammatory mediators, including IL-6, TNF-α, and IL-1β. Niclosamide provides a new therapeutic strategy for murine sepsis models by suppressing the inflammatory response through STAT3 inhibition.