• 대한본초학회지
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• 제24권3호
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• pp.79-86
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• 2009

Objectives : The present study investigated Inflammatory effect of Coptidis Rhizoma in lipopolysaccharideexposed rats and Raw 264.7 cells. Methods： The plasma concentration of IL-1$\beta$, IL-6 and TNF-$\alpha$ peaked at 5 h after LPS injection, and the values of the Coptidis Rhizoma extract groups were lower than those of the control group. In the increment of cytokines concentration at 2 h and 5 h after LPS injection, the Coptidis Rhizoma groups were lower than that of control group. The plasma concentration of IL-10 peaked at 5 h after LPS injection, and the values of the Coptidis Rhizoma extract groups were higher than those of the control group. In the increment of cytokines concentration at 2 h and 5 h after LPS injection, the Coptidis Rhizoma groups were higher than that of control group. Liver cytokines measurement was done at 5 h after LPS injection. The concentration of liver IL-1$\beta$ and IL-6 in the Coptidis Rhizoma groups was 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. Results： In the studies of lipopolysaccharide-exposed Raw 264.7 cells, the concentration of IL-1$\beta$, IL-6 and TNF-$\alpha$ in the lipopolysaccharide-exposed cells groups was higher than that of control group (normal group), and in the lipopolysaccharide-exposed cells groups, these values showed a tendency to decrease in the Coptidis Rhizoma groups. The concentration of IL-10 in the lipopolysaccharide-exposed cells groups was higher than that of control group (normal group), and in the lipopolysaccharide-exposed cells groups, the values showed a tendency to increase in the Coptidis Rhizoma groups. Conclusions： These results indicate that the Coptidis Rhizoma extracts have an functional material for Inflammatory activities.

• 한방비만학회지
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• 제16권2호
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• pp.85-91
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• 2016

목적: 본 연구는 황금추출물이 과산화지질을 장기간 급여한 흰쥐의 지질대사, 산화반응 및 전염증성 cytokine의 생산에 미치는 영향을 검토하기 위해 수행되었다. 방법: 10주 동안 흰쥐에게 과산화지질을 과량으로 급여하여 생체 내에 과잉의 지질을 축적시킨 후, 황금추출물을 6주간 급여하였다. 그 후, 각 처리군별로 지질대사, 산화반응 및 전염성 cytokine의 생산에 미치는 영향을 조사했다. 결과: 혈액 내 유리지방산, 총지질, 총콜레스테롤, low density lipoprotein-cholesterol과 간장 내 총지질, 총콜레스테롤이 황금추출물 처리군에서 하락했다. 혈액 및 간장의 thiobarbituric acid 농도가 황금추출물 처리군에서 하락했다. 간장 내 항산화효소들(glutathione peroxidase, liver catalase, liver superoxide dismutase)의 활성치가 황금처리군에서 상승하였다. 전염증성 cytokine(interleukin $[IL]-1{\beta}$, tumor necrosis $factor-{\alpha}$, IL-6)의 농도는 황금추출물 처리군에서 하락했다. 반면에 IL-10의 농도는 황금추출물 처리군에서 증가했다. 결론: 이상의 결과들을 종합해 보면, 황금 추출물은 과산화지질을 급여한 비만쥐의 지질대사, 항산화반응 및 항염증반응에 긍정적인 효과를 나타내었음을 인식시켜 준다.

• Journal of Ginseng Research
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• 제41권2호
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• pp.159-168
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• 2017

Background: Radiotherapy is one of the most important modalities in cancer treatment; however, normal tissue damage is a serious concern. Drug development for the protection or reduction of normal tissue damage is therefore a clinical issue. Herein, we evaluated the protective properties of Panax ginseng Meyer and its corresponding mechanisms. Methods: C56BL/6 mice were orally pretreated with P. ginseng water extract (PGE; 25 mg/kg, 50 mg/kg, or 100 mg/kg) or intraperitoneally injected melatonin (20 mg/kg) for 4 d consecutively, then exposed to 15-Gy X-ray radiation 1 h after the last administration. After 10 d of irradiation, the biological properties of hematoxicity, fat accumulation, histopathology, oxidative stress, antioxidant activity, pro-inflammatory cytokines, and apoptosis signals were examined in the hepatic tissue. Results: The irradiation markedly induced myelosuppression as determined by hematological analysis of the peripheral blood. Steatohepatitis was induced by X-ray irradiations, whereas pretreatment with PGE significantly attenuated it. Oxidative stress was drastically increased, whereas antioxidant components were depleted by irradiation. Irradiation also notably increased serum liver enzymes and hepatic protein levels of pro-inflammatory cytokines. Those alterations were markedly normalized by pretreatment with PGE. The degree of irradiation-induced hepatic tissue apoptosis was also attenuated by pretreatment with PGE, which was evidenced by a terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick-end labeling assay, western blotting, and gene expressions analysis, particularly of apoptotic molecules. Conclusion: We suggest that PGE could be applicable for use against radiation-induced liver injury, and its corresponding mechanisms involve the modulation of oxidative stress, inflammatory reactions, and apoptosis.

• Parasites, Hosts and Diseases
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• 제55권3호
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• pp.295-304
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• 2017

Opisthorchis viverrini infection induces chronic inflammation, and a minor proportion of infected individuals develop advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA). Inflammatory cytokines and/or their gene polymorphisms may link to these biliary pathologies. We therefore investigated associations among cytokine gene polymorphisms and cytokine production in 510 Thai cases infected with O. viverrini who presented with APF+ or APF-, as established by abdominal ultrasonography as well as in patients diagnosed with CCA. Levels of pro-inflammatory and anti-inflammatory cytokines were determined in culture supernatants after stimulation of peripheral blood mononuclear cells (PBMCs) with O. viverrini excretory-secretory (ES) products. Pro-inflammatory cytokines, IL-$1{\beta}$, IL-6, IFN-${\gamma}$, LT-${\alpha}$, and TNF-${\alpha}$ were significantly increased in CCA patients compared with non-CCA (APF- and APF+) cases. Polymorphisms in genes encoding IL-$1{\beta}$-511C/T, IL-6-174G/C, IFN-${\gamma}$+874T/A, LT-${\alpha}$+252A/G, and TNF-${\alpha}$-308G/A were then investigated by using PCR-RFLP or allele specific-PCR (AS-PCR) analyses. In the CCA cases, LT-${\alpha}$+252A/G and TNF-${\alpha}$-308G/A heterozygous and homozygous variants showed significantly higher levels of these cytokines than the wild type. By contrast, levels of cytokines in wild type of IFN-${\gamma}$+874T/A were significantly higher than the variants in CCA cases. IFN-${\gamma}$+874T/A polymorphisms were associated with advanced periductal fibrosis, whereas IL-6-174G/C polymorphisms were associated with CCA. To our knowledge, these findings provide the first demonstration that O. viverrini infected individuals carrying several specific cytokine gene polymorphisms are susceptible to develop fibrosis and CCA.

• 한방재활의학과학회지
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• 제21권1호
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• pp.35-46
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• 2011

Objectives : The present study investigated inflammatory effect of Rheum undulatum L. in lipopolysaccharide-exposed rats and Raw 264.7 cells. Methods : Male rats weighting $185.39{\pm}8.21g$ fed basal diet for 1 week and 32 rats were divided into a control group and 3 experimental groups. We fed a control group of rats a basal diet and administered normal saline(100 mg/kg, 1time/1day) for 6 weeks. And we fed basal diet and administered an extract of Rheum undulatum L.(100 mg/kg, 200 mg/kg, 300 mg/kg, 1time/1day) to each experimental group of rats. We measured the plasma concentration of $IL-1{\beta}$($interleukin-1{\beta}$), IL-6 and $TNF-{\alpha}$(tumor necrosis $factor-{\alpha}$), liver cytokines, Raw 264.7 macrophages cytokines. Results : The plasma concentration of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ peaked at 5h(hour) after LPS(lipopolysaccharides) injection, and the values of the Rheum undulatum L. extract groups were lower than those of the control group. In the increment of these cytokines concentration at 2h and 5h after LPS injection, the Rheum undulatum L. groups were lower than that of control group. The plasma concentration of IL-10 peaked at 5h after LPS injection, and the values of the Rheum undulatum L. extract groups were higher than those of the control group. In the increment of this cytokine concentration at 2h and 5h after LPS injection, the Rheum undulatum L. groups were higher than that of control group. Liver cytokines measurement was done at 5h after LPS injection. The concentration of liver $IL-1{\beta}$ and IL-6 in the Rheum undulatum L. groups was 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. In the studies of lipopolysaccharide-exposed Raw 264.7 cells, the concentration of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ in the lipopolysaccharide-exposed cells groups was higher than that of control group(normal group), and in the lipopolysaccharide-exposed cells groups, these values showed a tendency to decrease in the Rheum undulatum L. groups. The concentration of IL-10 in the lipopolysaccharide-exposed cells groups was higher than that of control group(normal group), and in the lipopolysaccharide-exposed cells groups, the values showed a tendency to increase in the Rheum undulatum L. groups. Conclusions : These results indicate that the Rheum undulatum L. extracts have an functional material for inflammatory activities.

• BMB Reports
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• 제55권4호
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• pp.166-174
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• 2022

Hepatic macrophages are key immune cells associated with the broad ranges of liver diseases including steatosis, inflammation and fibrosis. Hepatic macrophages interact with other immune cells and orchestrate hepatic immune circumstances. Recently, the heterogenous populations of hepatic macrophages have been discovered termed residential Kupffer cells and monocyte-derived macrophages, and identified their distinct population dynamics during the progression of various liver diseases. Liver injury lead to Kupffer cells activation with induction of inflammatory cytokines and chemokines, which triggers recruitment of inflammatory monocyte-derived macrophages. To understand liver pathology, the functions of different subtypes of liver macrophages should be regarded with different perspectives. In this review, we summarize recent advances in the roles of hepatic macrophages under liver damages and suggest hepatic macrophages as promising therapeutic targets for treating liver diseases.

• IMMUNE NETWORK
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• 제23권6호
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• pp.46.1-46.16
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• 2023

Autoimmune hepatitis (AIH) affects all age group and occurs mainly in women. Pyroptosis is a novel programmed cell death featured with cell bursting and release of proinflammatory cytokines. A deeper understanding of AIH pathogenesis will contribute to novel therapy for AIH patients. Here, we aimed to investigate the role of IL-17 in immune-mediated liver injury. The levels of cytokines were measured by ELISA, and mRNA levels of STAT3 and IFN gamma-inducible protein 16 (IFI16) were detected by PCR. Expressions of STAT3, IFI16, gasdermin D and cleaved caspase-1 were measured by western-blotting. Immunohistochemical staining and transmission electron microscopy were applied to evaluate liver histopathological changes of the treated mice. Our results showed that the levels of IFI16 was increased in hepatocytes treated with IL-17 protein, and further elevated after STAT3-overexpressed (STAT3-OE) lentivirus treatment. The levels of IFI16 were reduced in hepatocytes treated with IL-17 neutralizing Ab (nAb), but were significantly increased after STAT3-OE treatment. Pyroptosis was observed in hepatocytes treated with IL-17 protein, and further cell damage was observed after STAT3-OE lentivirus treatment. Liver damage was alleviated in mice treated with IL-17 nAb, however sever damage was experienced after STAT3-OE lentivirus treatment. A binding interaction between IFI16 and STAT3 was detected in IL-17 treated hepatocytes. Glutathione transaminase activity was enhanced in concanavalin A-induced AIH mice compared to the control group (p<0.01). IL-17 plays an important role in activating STAT3 and up-regulating IFI16, which may promote the pyroptosis in AIH-related liver injury through STAT3-IFI16 axis.

• Molecules and Cells
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• 제39권8호
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• pp.639-644
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• 2016

Discovery of non-invasive diagnostic and predictive biomarkers for acute rejection in liver transplant patients would help to ensure the preservation of liver function in the graft, eventually contributing to improved graft and patient survival. We evaluated selected cytokines and chemokines in the sera from liver transplant patients as potential biomarkers for acute rejection, and found that the combined detection of IL-10, IL-17, and CXCL10 at 1-2 weeks post-operation could predict acute rejection following adult liver transplantation with 97% specificity and 94% sensitivity.

• 동의생리병리학회지
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• 제25권6호
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• pp.982-988
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• 2011

This research seeks a basis for developing new anti-inflammatory medicine by investigating Cornus Walteri extract for its anti-inflammatory effects. After the injection of LPS in to rats with Cornus Walteri extract, its anti-inflammatory effects were compared among the treatment groups. The plasma concentration of IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ peaked at 5h after LPS injection, and the values of the Cornus Walteri extract groups were lower than those of the control group. In the increment of concentration of these cytokines at 2h and 5h after LPS injection, the Cornus Walteri groups were lower than that of control group. The plasma concentration of IL-10 peaked at 5h after LPS injection, and the values of the Cornus Walteri extract groups were higher than those of the control group. In the increment of cytokines concentration at 2h and 5h after LPS injection, the Cornus Walteri groups were higher than that of control group. Liver cytokines measurement was done at 5h after LPS injection. The concentration of liver IL-$1{\beta}$ and IL-6 in the Cornus Walteri groups was 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. In the studies of lipopolysaccharide-exposed Raw 264.7 cells, the concentration of IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ in the lipopolysaccharide-exposed cells groups was higher than that of control group (normal group). However, in lipopolysaccharide-exposed cells groups, they showed lower values than those of control group and these values showed a tendency to decrease in the Cornus Walteri groups. The concentration of IL-10 in the lipopolysaccharide-exposed cells groups was higher than that of control group (normal group), and among the lipopolysaccharide-exposed cells groups, all Cornus Walteri extract groups showed higher values than single lipopolysaccharide-exposed cells groups. This studies have shown that in vitro and in vivo Cornus Walteri extracts are significantly more sensitive to inflammatory cytokines and LPS induced lethality. We conclude that the Cornus Walteri extracts have an functional material for inflammatory activities.

• IMMUNE NETWORK
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• 제10권6호
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• pp.181-187
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• 2010

Excessive alcohol consumption is one of the critical causative factors leading to alcoholic liver disease (ALD). ALD is characterized by a wide spectrum of liver damage, ranging from simple uncomplicated liver steatosis (fatty liver) to steatohepatitis and liver fibrosis/cirrhosis. It has been believed that the obvious underlying cause for ALD is due to hepatocyte death induced by alcohol itself. However, recent sparkling studies have shown that diverse immune responses contribute to ALD because liver is enriched with numerous immune cells. Especially, a line of evidence has suggested that innate immune cells such as Kupffer cells and natural killer (NK)/NKT cells are significantly involved in the pathogenesis of ALD via production of pro-inflammatory cytokines and other mediators. Indeed, more interestingly, hepatic stellate cells (HSCs), known as a major cell inducing liver steatosis and fibrosis, can be killed by liver NK cells, which could be suppressed by chronic alcohol consumption. In this review, with the view of liver as predominant innate immune organ, we describe the pathogenesis of ALD in which what roles of innate immune cells are and how they are interacting with HSCs.