• Parasites, Hosts and Diseases
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• 제56권1호
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• pp.53-59
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• 2018

Tick saliva is critically important for continuous attachment to the host, blood feeding for days, and transmission of tick-borne pathogens. To characterize the patterns of inflammatory cytokine gene expression during its attachment and blood sucking time, peripheral blood samples of rabbits infested with Haemaphysalis longicornis ticks were collected at different intervals. Blood histamine concentration was evaluated as well as gene encoding IFN-${\gamma}$, TNF-${\alpha}$, IL-2, IL-6, IL-4, and IL-10 were compared with non-infested rabbits. Blood histamine concentration of tick-infested rabbits during fast feeding time was significantly higher than that of non-infested rabbits. In both nymph and adult tick infested rabbits, expression of TNF-${\alpha}$ and IFN-${\gamma}$ genes were decreased significantly (P<0.05), while expression of IL-4, IL-6, and IL-10 were increased 1.3 to 7 folds in adult infested rabbits with the exception of IL-6 that was significantly (P<0.05) decreased in nymph infested rabbits. IL-2 was not expressed in either nymph or adult infestation. H. longicornis saliva is capable of modulate host responses through a complex correlation with histamine and Th1, Th2 mediated cytokines that suppress the inflammatory responses directed toward inflammatory mediators introduced into the host during tick feeding.

• BMB Reports
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• 제48권3호
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• pp.172-177
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• 2015

Upregulation of pro-inflammatory mediators contributes to ${\beta}$-cell destruction and enhanced infiltration of immune cells into pancreatic islets during development of type 1 diabetes mellitus. In this study, we examined the regulatory effects and the mechanisms of action of celastrol against cytotoxicity and pro-inflammatory immune responses in the RINm5F rat pancreatic ${\beta}$-cell line stimulated with a combination of interleukin-1 beta, tumor necrosis factor-alpha, and interferon-${\gamma}$. Celastrol significantly restored cytokine-induced cell death and significantly inhibited cytokine-induced nitric oxide production. In addition, the protective effect of celastrol was correlated with a reduction in pro-inflammatory mediators, such as inducible nitric oxide synthase, cyclooxygenase-2, and CC chemokine ligand 2. Furthermore, celastrol significantly suppressed cytokine-induced signaling cascades leading to nuclear factor kappa B (NF-${\kappa}B$) activation, including $I{\kappa}B$-kinase (IKK) activation, $I{\kappa}B$ degradation, p65 phosphorylation, and p65 DNA binding activity. These results suggest that celastrol may exert its cytoprotective activity by suppressing cytokine-induced expression of pro-inflammatory mediators by inhibiting activation of NF-${\kappa}B$ in RINm5F cells.

• 동의생리병리학회지
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• 제16권4호
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• pp.768-773
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• 2002

Behcets disease is a systemic inflammatory disorder. The etiology and pathogenesis of Behcets disease has yet been fully elucidated but might involve immune dysfunction. Cytokines involved in the regulation of inflammatory reactions and immune responses may play a role in the pathogenesis of Behcets disease (BD). Onchungeum is an Oriental herbal medication, which has been successfully used in Korea for the treatment of BD. This report describes modulation effects of Onchungeum on cytokine production from phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) of Behcets patients by ELISA. Onchungeum significantly inhibited the production of pro-inflammatory cytokines. TNF-α and IL-1β, compared to absence of Onchungeum (by 52.3 1.4 % inhibition for TNF-α and 113.5 3.3 % for IL-1β, p < 0.001). Onchungeum also inhibited the production of IFN-γ, immunoregulatory Th1 cytokine, by 89.4 0.8 % (p < 0.001). The inhibitory effects of Onchungeum on cytokine production showed dose-dependent manner, and the pre-treatment of 1 mg/ml Onchungeum had better effects than immunosuppressive drug for treatment of BD, cyclosporin A. Our results suggest that Onchungeum treatment for Behcets disease patients may have pharmacologic activities and abilities of regulation of immune and inflammatory responses by cytokine modulation.

• 대한임상검사과학회지
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• 제48권3호
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• pp.176-182
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• 2016

대식세포에서 염증반응이 진행되면, interleukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) 등의 cytokine들이 발현되어 inducible nitric oxide synthase (iNOS), prostaglandin E2(PGE2) 등의 염증유발인자가 생성된다. 오가피, 우슬, 두충 각각의 추출물이 어느 정도의 항 염증 효능을 보이며 어떤 pro-inflammatory cytokine의 발현을 억제하는지에 대한 연구를 진행하였다. 오가피, 우슬, 두충은 물 추출하고 동결 건조시켰다. 각각의 추출물의 구성 성분들이 잘 추출되었는지 확인하기 위하여 지표물질인 acanthoside D, 20-hydroxyecdysone, pinoresinol diglucoside를 HPLC로 분석하였다. 항 염증 효능을 확인하기 위하여 lipopolysaccharide (LPS)로 RAW 264.7 세포주를 자극하여 염증 반응을 일으킨 상태에서 각각의 추출물을 농도 별로 처리하고 NO assay를 통해 항 염증 효능을 확인하였으며 real time PCR로 pro-inflammatory cytokine들의 발현량을 측정하였다. 결과적으로 각각의 추출물은 지표성분들이 검출되었으며 오가피와 우슬이 두충보다 NO assay에서 높은 활성을 보였다. Cytokine 발현량 측정에서는 오가피와 우슬은 iNOS와 IL-6의 발현을 억제하였고, 우슬은 TNF-${\alpha}$의 발현을 억제하였다. 우리나라는 전통적으로 약재를 조합하여 처방하여 왔다. 본 연구는 관절염에 전통적으로 사용해 오던 약재들이 어떤 기전에 의하여 항 염증 반응을 보이는지 확인하고 이들을 조합하여 사용하였을 때 어떤 근거에 의하여 시너지 효능을 보이는지 확인하였다.

• BMB Reports
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• 제53권12호
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• pp.640-645
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• 2020

Suppressors of cytokine signaling (SOCS) exhibit diverse anti-inflammatory effects. Since ROS acts as a critical mediator of inflammation, we have investigated the anti-inflammatory mechanisms of SOCS via ROS regulation in monocytic/macrophagic cells. Using PMA-differentiated monocytic cell lines and primary BMDMs transduced with SOCS1 or shSOCS1, the LPS/TLR4-induced inflammatory signaling was investigated by analyzing the levels of intracellular ROS, antioxidant factors, inflammasome activation, and pro-inflammatory cytokines. The levels of LPS-induced ROS and the production of pro-inflammatory cytokines were notably down-regulated by SOCS1 and up-regulated by shSOCS1 in an NAC-sensitive manner. SOCS1 up-regulated an ROS-scavenging protein, thioredoxin, via enhanced expression and binding of NRF-2 to the thioredoxin promoter. SOCS3 exhibited similar effects on NRF-2/thioredoxin induction, and ROS downregulation, resulting in the suppression of inflammatory cytokines. Notably thioredoxin ablation promoted NLRP3 inflammasome activation and restored the SOCS1-mediated inhibition of ROS and cytokine synthesis induced by LPS. The results demonstrate that the anti-inflammatory mechanisms of SOCS1 and SOCS3 in macrophages are mediated via NRF-2-mediated thioredoxin upregulation resulting in the downregulation of ROS signal. Thus, our study supports the anti-oxidant role of SOCS1 and SOCS3 in the exquisite regulation of macrophage activation under oxidative stress.

• 대한한방내과학회지
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• 제25권1호
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• pp.46-58
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• 2004

Objectives : This study was designed to investigate the effects of Injinchunggan-tang(Yinchenqinggan-tang) on the expression of inflammatory cytokine genes and proteins in kupffer cells. Materials and Methods : The mRNA expression level and protein secretion level were measured using quantitative RT-PCR and ELISA assay respectively in Injinchunggan-tang-treated and untreated kupffer cells after exposed to ethanol, acetaldehyde and lipopolysaccharide. Results : Injinchunggan-tang(Yinchenqinggan-tang) reduced mRNA expression level and protein secretion level of $TNF-{\alpha},\;TGF-{\beta}1,\;IL-1{\beta},\;IL-6,\;IL-8$ that are induced by ethanol, acetaldehyde and lipopolysaccharide in kupffer cells and that mediate inflammation and fibrosis of liver. Conclusion : The result indicates that Injinchunggan-tang (Yinchenqinggan-tang) blocks alcohol-induced liver injury and protects liver by reducing production of inflammatory cytokines.

• 대한의생명과학회지
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• 제28권3호
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• pp.192-194
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• 2022

The trophic factor Neuregulin-1 (NRG-1) plays a critical role in the development of the peripheral nervous system and the repair of nerve injuries. The regulation of neutrophil apoptosis by cytokine secretion from structural cells is an important process in inflammatory diseases, including asthma. This study aimed to investigate the relationship between NRG-1 and the alteration of neutrophil apoptosis by the regulation of cytokine release in the human lung epithelial BEAS-2B cells. Tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) induce the increase in the release of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1). NRG-1 alone had no effect on the secretion of IL-6, IL-8, and MCP-1. However, co-treatment of TNF-α and IFN-γ with NRG-1 inhibited the secretion of IL-6, IL-8, and MCP-1 that had been increased by TNF-α and IFN-γ. Treatment with NRG-1 did not have a direct effect on neutrophil apoptosis. Co-treatment of TNF-α and IFN-γ with NRG-1 was not effective on suppression of neutrophil apoptosis due to TNF-α and IFN-γ. The supernatant of BEAS-2B cells after co-treatment of TNF-α and IFN-γ with NRG-1 suppressed the inhibition of neutrophil apoptosis that had been caused due to the supernatant treated with TNF-α and IFN-γ. Taken together, NRG-1 has an anti-inflammatory effect in an inflammatory milieu by the regulation of cytokine secretion and neutrophil apoptosis.

• 한방안이비인후피부과학회지
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• 제29권3호
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• pp.95-105
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• 2016

Objectives : Allergic diseases have a various symptoms of hyperresponsiveness and recently hyperresponsive reaction in the chronic phase is reported as the important mechanisms. Cheonggisan(CGS) is used in oriental clinics for curing various skin diseases due to effect of controlling of pruritus. There have been studies on the anti-allergic effect and anti-inflammatory effect of CGS, but there had no study of anti-allergic effects in allergic late inflammation of CGS, so we aimed to find out the effects of CGS in allergic late inflammation in our study.Methods : To investigate the anti-allergy effect and anti-inflammatory effect of CGS, RAW 264.7 macrophage cells and CSG water-extracts were used. Cytotoxic effect of CSG was examined by MTT assay, an oxidative product of NO was measured in the culture medium by the Griess reagent assay. The level of prostaglandin E2(PGE2) was measured by competitive enzyme-linked immunoassay. Cytokine(PGE2, IL-1β, IL-6, TNF-α) was measured by Bio-Plex suspension assay system and quantitative multiplexed cytokine/chemokine assay.Results : We investigated that there was no cytotoxic effect of CGS water-extract at any levels of concentration on RAW 264.7 macrophage cells by MTT assay. CGS water-extracts significantly suppressed the levels of the inflammatory mediators such as NO and PGE2, cytokine of IL-1β, TNF-α at the level of 400 ㎍/㎖ CGS concentration. But there was no significant effect on IL-6 production suppression.Conclusions : These results suggest that CSG water-extract has and anti-inflammatory effects in allergic reaction. These properties may contribute to the allergic diseases and inflammatory related disease care.

• 대한한의학회지
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• 제24권3호
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• pp.84-95
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• 2003

Objective : This study was carried out to investigate the effects of Kamisopunghwalhyeol-tang (Jiaweishujenghuoxie-tang; Kami-SPHHT) on the immunity responses of the Synoviocytes isolated from the patients on rheumatoid arthritis. Methods : Cells were stimulated by $Interleukin-1{\beta}$ and Tumor Necrosis $Factor-{\alpha}$ in the presence or absence of Kami-SPHHT, and then induced cytokine mRNA levels were determined by RT-PCR and real-time quantitative RT-PCR. Results : Levels of $IL-1{\beta},{\;}IL-6,{\;}TNF-{\alpha}$, COX-2, and NOS II mRNA expressions significantly decreased in Kami-SPHHT treated cells compared to non-treated control cells. Also, DNA-binding activity of $NF-{\kappa}B$ and AP-l decreased in Kami- SPHHT treated hFLSs. Conclusion : These results suggest that Kami-SPHHT may be involved in anti-inflammatory reactions by inducing cytokine gene expression in synoviocytes, and further in vivo examination on its efficacy can provide potential application for the treatment of rheumatoid arthritis.

• 대한한방부인과학회지
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• 제30권2호
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• pp.1-15
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• 2017

Objectives: The object of this study was to identify the anti-inflammatory effects of Patrinia scabiosaefolia aqueous extract (PSE). Methods: RAW 264.7 cells were pre-treated with PSE and then incubated with or without lipopolysaccharide (LPS). Cell viability, production of nitric oxide (NO), secretion of pro-inflammatory cytokine, activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-${\kappa}B$) were measured. In addition, we observed mice survival rate after LPS and their cytokine levels of serum. We also observed inflammatory and hemorrhagic change on the histological sections of the liver. Results: PSE inhibited LPS-induced NO production, interleukin (IL)-6 secretion, c-Jun NH2-terminal kinase (JNK) and NF-${\kappa}B$ activation. In addition, PSE reduced the death rate of LPS-induced mice and IL-6 production on the serum of mice. PSE inhibited inflammation and hemorrhage on liver tissue as well. Conclusions: The results suggest that PSE have anti-inflammatory effects by inhibited NF-${\kappa}B$ and JNK activation, IL-6 secretion, and NO production. So PSE may be effective treatment for the inflammatory disease.