• Yonsei Medical Journal
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• 제59권9호
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• pp.1064-1071
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• 2018

Purpose: To explore the influence of S100 calcium binding protein A4 (S100A4) knockout (KO) on methionine-choline-deficient (MCD) diet-induced non-alcoholic fatty liver disease (NAFLD) in mice. Materials and Methods: S100A4 KO mice (n=20) and their wild-type (WT) counterparts (n=20) were randomly divided into KO/MCD, Ko/methionine-choline-sufficient (MCS), WT/MCD, and WT/MCS groups. After 8 weeks of feeding, blood lipid and liver function-related indexes were measured. HE, Oil Red O, and Masson stainings were used to observe the changes of liver histopathology. Additionally, expressions of S100A4 and proinflammatory and profibrogenic cytokines were detected by qRT-PCR and Western blot, while hepatocyte apoptosis was revealed by TUNEL staining. Results: Serum levels of aminotransferase, aspartate aminotransferase, triglyceride, and total cholesterol in mice were increased after 8-week MCD feeding, and hepatocytes performed varying balloon-like changes with increased inflammatory cell infiltration and collagen fibers; however, these effects were improved in mice of KO/MCD group. Meanwhile, total NAFLD activity scores and fibrosis were lower compared to WT+MCD group. Compared to WT/MCS group, S100A4 expression in liver tissue of WT/MCD group was enhanced. The expression of proinflammatory ($TGF-{\alpha}$, $IL-1{\beta}$, IL-6) and profibrogenic cytokines ($TGF-{\beta}1$, COL1A1, ${\alpha}-SMA$) in MCD-induced NAFLD mice were increased, as well as apoptotic index (AI). For MCD group, the expressions of proinflammatory and profibrogenic cytokines and AI in KO mice were lower than those of WT mice. Conclusion: S100A4 was detected to be upregulated in NAFLD, while S100A4 KO alleviated liver fibrosis and inflammation, in addition to inhibiting hepatocyte apoptosis.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제15권2호
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• pp.74-78
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• 2012

With a markedly increased prevalence of obesity, non-alcoholic fatty liver disease (NAFLD) now becomes the most common cause of chronic liver disease in both adults and children. The etiology and pathogenesis of NAFLD are multifactorial and remain incompletely understood. According to the "two-hit" theory, inflammatory cytokines and adipokines are activated by oxidative stress and they are involved in insulin resistance, necroinflammatory steatohepatitis and fibrosis. This review discusses the latest updates on the role of some of important inflammatory adipokines and cytokines in the pathogenesis of NAFLD with an emphasis on their potential therapeutic implications.

• Radiation Oncology Journal
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• 제18권3호
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• pp.205-213
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• 2000

Purpose : 백서의 간에서 나타나는 방사선조사에 의한 조직손상에서 IL-1, IL-4, IL-6, TNF 등의 cyokine과 apoptosis와의 상관관계를 알아보고자 하였다. 대상 및 방법 : 백서의 전신에 8 Gy의 방사선조사 후 각 1일, 3일, 5일, 7일, 14일에 간 조직의 변화를 현미경으로 관찰하고, apoptosis의 발현빈도를 확인하였으며, IL-1, IL-4, IL-6군 및 TNF 등의 cytoklne에 대해서 면역조직화학염색 방법과, 간 조직과 혈액에서의 IL-6의 생물학적 활성도 측정 및 방사선 면역측정 등의 실험을 하였다. 결과 : 방사선조사에 의한 간 손상은 광학현미경 소견상 방사선조사 후 1일부터 관찰되어, 3일과 5일에 염증세포의 침윤과 함께 가장 심하게 나타났고, 7일 이후부터는 섬유화가 시작되었다. Apoptosis의 발현빈도는 광학현미경 소견과 in situ detection method 모두에서 방사선조사 후 1일에 가장 높게 나타났다. 면역조직화학 염색소견상, IL기과 TNF의 발현은 조사 후 1일과 3일에 보였고, IL-4는 모든 군에서 발현되지 않았다. IL순는 방사선조사 후 1일과 3일에 강양성으로 나타난 후 점차 감소하였고, 간 조직과 혈액에서의 IL푼의 생물학적 활성도와 방사선면역측정에서도 방사선조사 후 1일에 가장 높고 이후 점차 감소하였다. 결론 : 간에 방사선조사를 시행한 결과 IL-1, IL-6군 및 TNF와 같은 cytokine의 발현이 증가되었으며, 이들 cylokine의 분비가 apoptosis를 유도함으로써 apoptosls가 방사선조사에 의한 간 손상에 중요한 기전의 하나로 작용할 것으로 생각된다.

• Asian-Australasian Journal of Animal Sciences
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• 제29권1호
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• pp.1-15
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• 2016

Since the discovery of leptin secreted from adipocytes, specialized tissues and cells have been found that secrete the several peptides (or cytokines) that are characterized to negatively and positively regulate the metabolic process. Different types of adipokines, hepatokines, and myokines, which act as cytokines, are secreted from adipose, liver, and muscle tissue, respectively, and have been identified and examined for their physiological roles in humans and disease in animal models. Recently, various studies of these cytokines have been conducted in ruminants, including dairy cattle, beef cattle, sheep, and goat. Interestingly, a few cytokines from these tissues in ruminants play an important role in the post-parturition, lactation, and fattening (marbling) periods. Thus, understanding these hormones is important for improving nutritional management in dairy cows and beef cattle. However, to our knowledge, there have been no reviews of the characteristics of these cytokines in beef and dairy products in ruminants. In particular, lipid and glucose metabolism in adipose tissue, liver tissue, and muscle tissue are very important for energy storage, production, and synthesis, which are regulated by these cytokines in ruminant production. In this review, we summarize the physiological roles of adipokines, hepatokines, and myokines in ruminants. This discussion provides a foundation for understanding the role of cytokines in animal production of ruminants.

• 대한의생명과학회지
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• 제16권3호
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• pp.139-149
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• 2010

The present study was carried out to elucidate whether an environmental strain of Cryptococcus neoformans (environmental C. neoformans) isolated from an environmental source in a park of Busan has an acute pathophysiological effect in rats. On the second day after peritoneal inoculation of environmental C. neoformans, adverse effects occurred from the viewpoint of hematology and biochemistry. Eosinophil damages and crystal formations were found in the blood. Disturbances in cytokines production were observed in the cerebral and pulmonary tissues. Fungal budding existed in the brain, lung, liver and kidney. Tissue injury findings such as inflammation, leukocyte infiltration, bleeding, or degeneration were found in the brain, lung, liver and kidney. The present data suggest that the environmental C. neoformans can cause systematically harmful effects even for short periods of infection (two days of cryptococcal infection) and the adverse effects are summarized as immune derangements and biochemical and/or histological dysfunction and injury on major organ such as the brain, lung, liver and kidney in the immunocompetent hosts. Further studies should be focused on comparing the differences between environmental and clinical strains of C. neoformans.

• 대한한방내과학회지
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• 제31권2호
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• pp.365-371
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• 2010

The present study investigated the anti-inflammatory effect of Jakyakgamcho-tang in lipopolysaccharide-exposed rats. The plasma concentration of IL-$1\beta$, IL-6 and TNF-$\alpha$ peaked at 5hrs after LPS injection, and these values of the 300 mg/kg Jakyakgamcho-tang group were lower than those of the control group. The plasma concentration of IL-10 peaked at 5hrs after LPS injection and the values of the Jakyakgamcho-tang groups were higher than those of the control group. In the liver cytokines measurement was done at 5hrs after LPS injection. The concentrations of liver IL-$1\beta$ and IL-6 in the 300 mg/kg Jakyakgamcho-tang were lower than that of the control group. The concentrations of liver TNF-$\alpha$, and IL-10 showed no significant differences among all the treatment groups. These results indicate that the Jakyakgamcho-tang has anti-inflammatory activities.

• 약학회지
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• 제43권2호
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• pp.198-207
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• 1999

The aim of the present investigation was to examine whether YH439, a hepatoprotective agent, exerts protective effect against hepatotoxicity and reduces the production of cytokines and NO in lipopolysaccharide (LPS)-primed rats with carbon tetrachloride ($CCl_4$). Administration of LPS following a single dose of CCl4 injection resulted in remarkable elevations of the serum $TNF{\alpha},{\;}IL-l{\beta$ and IL-6 level. The serum NO level was moderately elevated and severe liver damage was evidenced by increases in serum alanine aminotransferase (ALT) and sorbitol dehydrogenase (SDH) activities. YH439 decreased the levels of TNF, $IL-l{\beta}$, IL-6, ALT, SDH as well as NO in the serum elevated by CCl4+LPS in a dose-dependent manner. Inducible nitric oxide synthase (iNOS) level was decreased in the liver of rats treated with YH439. The increased iNOS activity induced by LPS and $interferon-{\gamma}$ was significantly decreased in RAW 264.7 cells by YH439 treatment. YH439 increased the GSH level decreased by $CCl_4+LPS$ and suppressed the ratio of GSSG/GSH. The reduction of hepatotoxicity by YH439 may associated with the decrease in the production of cytokines as well as suppression of iNOS protein in conjunction with an increase in the GSH level.

• 한방재활의학과학회지
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• 제24권2호
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• pp.1-13
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• 2014

Objectives The purpose of this study was to investigate the effects of Cheunggihwadamhwan (CGHDH) extract on lowering lipid, antioxidation and production of proinflammatory cytokines in rats fed on high fat diet. Methods 40 Male Sprague-Dawley rats were fed on high fat diet for 8 weeks and 32 rats (above 400 g) were randomly divided into 4 groups (8 mice in each group) : control group, 100 mg/Kg CGHDH group, 200 mg/Kg CGHDH group, 300 mg/Kg CGHDH group. We fed a control group of rats a basal diet and administered normal saline(100 mg/kg, 1 time/1 day) for 4 weeks. And We fed each experimental group of rats basal diet and administered an extract of Cheunggihwadamhwan extracts (100 mg/kg, 200 mg/kg, 300 mg/kg, 1 time/1 day) for 4 weeks. At the end of the experiment, the rats were sacrificed to determine their chemical composition. We measured lipid in plasma and liver, concentration of proinflammatory cytokines, antioxidative activity and gene expression. The gene expression level was investigated by the way of reverse transcription-polymerase chain reaction (RT-PCR). Results 1. Concentration of plasma FFA, plasma TG, plasma total cholesterol and plasma LDL-cholesterol showed a significant decrement in Cheunggihwadamhwan groups. However, concentration of plasma HDL-cholesterol showed a significant increment in 200, 300 mg/kg Cheunggihwadamhwan groups. 2. Concentration of liver total cholesterol and liver TG showed a significant decrement in Cheunggihwadamhwan groups. 3. Concentration of plasma TBARS showed a significant decrement in all Cheunggihwadamhwan groups. Concentration of liver TBARS showed a significant decrement in 200, 300 mg/kg Cheunggihwadamhwan groups. Concentration of liver GSH-Px, SOD and CAT showed a tendency to decrease in all Cheunggihwadamhwan groups. 4. Concentration of plasma IL-$1{\beta}$, plasma IL-6, TNF-$\alpha$ and NO, showed a tendency to decrease in all Cheunggihwadamhwan groups. Concentration of plasma IL-10 showed a tendency to increase in all Cheunggihwadamhwan groups. 5. In the analysis of reverse transcription-polymerase chain reaction (RT-PCR), the gene expression of Apo-B and Apo-E in the Cheunggihwadamhwan groups showed a low expression than that of control group. The ratio of Apo-B expression per $\beta$-actin expression in the showed a significant decrement in all Cheunggihwadamhwan groups. The ratio of Apo-E expression per $\beta$-actin expression in the showed a significant decrement in 300 mg/kg Cheunggihwadamhwan groups. Conclusions According to this study, the extract of Cheunggihwadamhwan showed a positive effect of lowering lipid, antioxidation and a control of producing proinflammatory cytokines.

• 대한의생명과학회지
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• 제19권2호
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• pp.158-163
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• 2013

Cholestatic liver is associated with hepatic inflammation and elevated proinflammatory cytokines. Recent studies indicate that certain cytokines can modulate bile secretion. In the present study, we have examined the role of interleukin (IL-2) on the bile secretion by a combination of study models. To examine the relevance of IL-2 on bile secretion, the expression of IL-2 and IL-2 receptor (IL-2R) of isolated normal and bile duct ligated (BDL) rats cholangiocytes was first measured by RT-PCR. In BDL rats, the expression of IL-2 and IL-2R was significantly increased compared with normal rats. To study the effect of IL-2 on bile secretion, bile flow was measured in normal and BDL rats. At the level of cholangiocytes, secretory responses of isolated bile duct unit (IBDU)s were quantified by videomicroscopy. The administrations of IL-2 had no significant effect on basal bile secretion in normal and BDL rats. There was no significant effect of IL-2 on basal bile ductular secretion as evidenced by no significant difference in luminal area of the IBDUs perfusedwith 100 pM of IL-2 from those of albumin carrier control. However, the secretin-stimulated bile ductular secretion was significantly (P < 0.01) inhibited by $34{\pm}4%$ (normal, n = 12), $21{\pm}5.3%$ (BDL 2 wk, n = 12) and $15{\pm}5.2%$ (BDL 4 wk, n = 12) with the co-administration of IL-2. As with other cytokines, physiologically relevant concentration of IL-2 can significantly inhibit secretin-stimulated bile ductular secretion. These findings support the important roles of cytokines in modulating bile secretion and may contribute to the cholestasis seen in cholestatic liver diseases.

• 대한한방부인과학회지
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• 제34권4호
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• pp.12-29
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• 2021

Objective: This study was performed to investigate the inhibitory effect of Cheongpochukeo-tang (CCT) on lipopolysaccharide (LPS)-induced inflammation model. Methods: RAW 264.7 cells were pre-treated with CCT and incubated with LPS (500 ng/ml) after 1 hour. Cell viability was measured by MTT assay to figure out cytotoxicity of CCT. The production of nitric oxide and mRNA expression of pro-inflammatory cytokine were measured. And the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) were examined to figure out molecular mechanisms of CCT's anti-inflammatory effects. In addition, mice survival rate and cytokine levels of serum were observed after treated with CCT. And mice liver tissues were observed and their cytokines levels in liver tissue were measured. Results: CCT did not have cytotoxic effect in RAW 264.7 cells. It inhibited LPS-induced nitric oxide (NO) production, but showed an increase in NO by itself at 2 mg/ml concentration. CCT inhibited mRNA expression of IL-1β, IL-6, TNF-α in a dose dependant and the activaton of MAPKs and NF-κB. In addition, CCT reduced mortality in the LPS-induced mouse model and inhibited production of cytokines in mouse serum and liver tissue. Conclusion: The results suggest that CCT could reduce LPS-induced inflammation by inhibiting MAPKs and NF-κB activaton, NO production, and pro-inflammatory cytokines secretion. Thereby, CCT could be effective medicine for the inflammatory disease.