• 대한미생물학회지
• /
• 제35권1호
• /
• pp.41-48
• /
• 2000

Bacteroides fragilis and Escherichia coli, normal colonic inhabitants, are the most frequently isolated bacteria in infected tissues, particularly in intraabdominal abscesses. This study was designed to determine whether enteric bacteria may alter the B. fragilis-induced expression of pro inflammatory cytokines in mouse peritoneal tissue (MPT). After C57BL/6 mice were inoculated with abscess-forming mixture containing B. fragilis in the presence or absence of E. coli, RNA was extracted from MPT. Expression of interleukin (IL)-$1{\alpha}$ and tumor necrosis factor $(TNF){\alpha}$ mRNA was assessed using RT-PCR and standard RNA. Each cytokine protein was also measured by ELISA. The co-inoculation of E. coli into mouse peritoneal cavity advanced the onset of abscess development by B. fragilis infection. When mouse was co-infected with E. coli and B. fragilis intraperitoneally, there was a synergistic increase in the expression of IL-$1{\alpha}$ and $TNF{\alpha}$ mRNA in MPT and this was paralleled by increased cytokine protein secretion. Mixed inoculation of heat-killed E. coli and B. fragilis did not cause a synergistic increase in those cytokine mRNA expression. These results suggest that enteric bacteria may significantly affect proinflammatory cytokine signal produced by host peritoneal cavity in response to B. fragilis infection.

• 약학회지
• /
• 제60권1호
• /
• pp.21-28
• /
• 2016

Systemic lupus erythematosus (SLE) is characterized by dysregulatory production of proinflammatory cytokines and helper T (Th) cytokine-dependent autoantibody production. This study aims to investigate the protective effect of baicalin on the dysregulatory production of proinflammatory cytokines and Th cytokines in pristane-induced lupus mice. Mice were received i.p. a single injection of 0.5 ml of pristane, and then, later about 3 months, were used as a pristane-induced lupus model. The pristane-induced lupus mice were administrated orally with baicalin 50 mg/kg once in a day for 10 days. Immune cells obtained from the pristane-primed lupus control group (lupus control) and baicalin-treated pristaneprimed lupus mouse group (BAC lupus) were cultured for 24 h or 36 h with/without mitogens. These results demonstrated that LPS-induced production of macrophage and splenic TNF-${\alpha}$ and Con A-induced production of thymic IFN-${\gamma}$ were attenuated in BAC lupus compared to lupus control, while LPS-stimulated production of macrophage IL-10, Con A-stimulated production of splenic IL-10 and, $PGE_2$-reduced production of splenic IFN-${\gamma}$ enhanced. Therefore, these findings suggest that baicalin may protect from autoimmunity and disease activity in lupus via modulatory effect of proinflammatory cytokine overproduction and Th cytokine imbalance.

• Bulletin of the Korean Chemical Society
• /
• 제31권12호
• /
• pp.3561-3566
• /
• 2010

Interleukin 32 (IL-32) is a recently identified cytokine that induces major proinflammatory cytokines such as $TNF{\alpha}$ and IL-$1{\beta}$, which play an important role in chronic inflammatory diseases. To antagonize the biological function of IL-32 in cells, we generated RNA aptamers that could bind specifically to IL-32 protein. The highest affinity aptamer, AC3-3, successfully antagonized IL-32 by abolishing the induction of $TNF{\alpha}$ in the human lung carcinoma cells expressing IL-32. This aptamer could be used as a potent and selective antagonist against IL-32 to further elucidate the roles of IL-32 in chronic inflammatory diseases, as well as a therapeutic agent.

• The Korean Journal of Physiology and Pharmacology
• /
• 제20권4호
• /
• pp.415-424
• /
• 2016

Berberine is an isoquinoline alkaloid found in Rhizoma coptidis, and elicits anti-inflammatory effects through diverse mechanisms. Based on previous reports that activating transcription factor-3 (ATF-3) acts as a negative regulator of LPS signaling, the authors investigated the possible involvement of ATF-3 in the anti-inflammatory effects of berberine. It was found berberine concentration-dependently induced the expressions of ATF-3 at the mRNA and protein levels and concomitantly suppressed the LPS-induced productions of proinflammatory cytokines ($TNF-{\alpha}$, IL-6, and $IL-1{\beta}$). In addition, ATF-3 knockdown abolished the inhibitory effects of berberine on LPS-induced proinflammatory cytokine production, and prevented the berberine-induced suppression of MAPK phosphorylation, but had little effect on AMPK phosphorylation. On the other hand, the effects of berberine, that is, ATF-3 induction, proinflammatory cytokine inhibition, and MAPK inactivation, were prevented by AMPK knockdown, suggesting ATF-3 induction occurs downstream of AMPK activation. The in vivo administration of berberine to mice with LPS-induced endotoxemia increased ATF-3 expression and AMPK phosphorylation in spleen and lung tissues, and concomitantly reduced the plasma and tissue levels of proinflammatory cytokines. These results suggest berberine has an anti-inflammatory effect on macrophages and that this effect is attributable, at least in part, to pathways involving AMPK activation and ATF-3 induction.

• The Korean Journal of Physiology and Pharmacology
• /
• 제25권4호
• /
• pp.307-319
• /
• 2021

Dysregulation of the Wnt pathway causes various diseases including cancer, Parkinson's disease, Alzheimer's disease, schizophrenia, osteoporosis, obesity and chronic kidney diseases. The modulation of dysregulated Wnt pathway is absolutely necessary. In the present study, we evaluated the anti-inflammatory effect and the mechanism of action of Wnt-C59, a Wnt signaling inhibitor, in lipopolysaccharide (LPS)-stimulated epithelial cells and macrophage cells. Wnt-C59 showed a dose-dependent anti-inflammatory effect by suppressing the expression of proinflammatory cytokines including IL6, CCL2, IL1A, IL1B, and TNF in LPS-stimulated cells. The dysregulation of the Wnt/β-catenin pathway in LPS stimulated cells was suppressed by WntC59 treatment. The level of β-catenin, the executor protein of Wnt/β-catenin pathway, was elevated by LPS and suppressed by Wnt-C59. Overexpression of β-catenin rescued the suppressive effect of Wnt-C59 on proinflammatory cytokine expression and nuclear factor-kappa B (NF-κB) activity. We found that the interaction between β-catenin and NF-κB, measured by co-immunoprecipitation assay, was elevated by LPS and suppressed by Wnt-C59 treatment. Both NF-κB activity for its target DNA binding and the reporter activity of NF-κB-responsive promoter showed identical patterns with the interaction between β-catenin and NF-κB. Altogether, our findings suggest that the anti-inflammatory effect of Wnt-C59 is mediated by the reduction of the cellular level of β-catenin and the interaction between β-catenin and NF-κB, which results in the suppressions of the NF-κB activity and proinflammatory cytokine expression.

• Biomolecules & Therapeutics
• /
• 제31권1호
• /
• pp.27-39
• /
• 2023

Extensive research supported the therapeutic potential of curcumin, a naturally occurring compound, as a promising cytokine-suppressive anti-inflammatory drug. This study aimed to investigate the synergistic anti-inflammatory and anti-cytokine activities by combining 6-shogaol and 10-shogaol to curcumin, and associated mechanisms in modulating lipopolysaccharides and interferon-γ-induced proinflammatory signaling pathways. Our results showed that the combination of 6-shogaol-10-shogaolcurcumin synergistically reduced the production of nitric oxide, inducible nitric oxide synthase, tumor necrosis factor and interlukin-6 in lipopolysaccharides and interferon-γ-induced RAW 264.7 and THP-1 cells assessed by the combination index model. 6-shogaol-10-shogaol-curcumin also showed greater inhibition of cytokine profiling compared to that of 6-shogaol-10-shogaol or curcumin alone. The synergistic anti-inflammatory activity was associated with supressed NFκB translocation and downregulated TLR4-TRAF6-MAPK signaling pathway. In addition, SC also inhibited microRNA-155 expression which may be relevant to the inhibited NFκB translocation. Although 6-shogaol-10-shogaol-curcumin synergistically increased Nrf2 activity, the anti-inflammatory mechanism appeared to be independent from the induction of Nrf2. 6-shogaol-10-shogaol-curcumin provides a more potent therapeutic agent than curcumin alone in synergistically inhibiting lipopolysaccharides and interferon-γ induced proinflammatory mediators and cytokine array in macrophages. The action was mediated by the downregulation of TLR4/TRAF6/MAPK pathway and NFκB translocation.

• BMB Reports
• /
• 제41권11호
• /
• pp.814-819
• /
• 2008

Interleukin-32 (IL-32) induces a variety of proinflammatory cytokines and chemokines. The IL-32 transcript was reported originally in activated T cells; subsequently, it was demonstrated to be abundantly expressed in epithelial and endothelial cells upon stimulation with inflammatory cytokines. IL-32 is regulated robustly by other major proinflammatory cytokines, thereby suggesting that IL-32 is crucial to inflammation and immune responses. Recently, an IL-32$\alpha$-affinity column was employed in order to isolate an IL-32 binding protein, neutrophil proteinase 3 (PR3). Proteinase 3 processes a variety of inflammatory cytokines, including TNF$\alpha$, IL-$1{\beta}$, IL-8, and IL-32, thereby enhancing their biological activities. In the current study, we designed four PR3-cleaved IL-32 separate domains, identified by potential PR3 cleavage sites in the IL-32$\alpha$ and $\gamma$ polypeptides. The separate domains of the IL-32 isoforms $\alpha$ and $\gamma$ were more active than the intrinsic $\alpha$ and $\gamma$ isoforms. Interestingly, the N-terminal IL-32 isoform $\gamma$ separate domain evidenced the highest levels of biological activity among the IL-32 separate domains.

• Preventive Nutrition and Food Science
• /
• 제19권3호
• /
• pp.156-163
• /
• 2014

We investigated the effects of a high-protein diet and resveratrol supplementation on immune cells changes induced by abdominal irradiation in rats. Female Wistar rats were divided into 5 groups: 1) control diet, 2) control diet with irradiation 3) 30% high-protein diet with irradiation, 4) normal diet with resveratrol supplementation and irradiation, and 5) 30% high-protein diet with resveratrol supplementation and irradiation. We measured blood protein and albumin concentrations, lipid profiles, white blood cell (WBC) counts, proinflammatory cytokine production, and splenocyte proliferation in rats that had been treated with a 17.5 Gy dose of radiation 30 days prior. A high-protein diet affected plasma total cholesterol and very low density lipoprotein-cholesterol levels, which were increased by the radiation treatment. In addition, the lymphocyte percentage and immunoglobulin M (IgM) concentration were increased, and the neutrophil percentage was decreased in rats fed a high-protein diet. Resveratrol supplementation decreased the triglyceride (TG) level, but increased the IgM concentration and splenocyte proliferation. Proinflammatory cytokine production was lower in rats fed a high-protein diet supplemented with resveratrol than in rats fed a control diet. The results of the present study indicate that high-protein diets, with or without resveratrol supplementation, might assist with recovery from radiation-induced inflammation by modulating immune cell percentages and cytokine production.

• Fisheries and Aquatic Sciences
• /
• 제10권1호
• /
• pp.1-7
• /
• 2007

The induction of cellular and humoral immunity and cytokine gene expression by synthetic CpG oligodexoynucleotides (CpG-ODNs) has not been investigated systematically in olive flounder Paralichthys olivaceus in vivo. We optimized the proper concentration of CpG-ODNs using an in vitro assay for the superoxide anion $(O_2^-)$. CpG-ODNs induced $O_2^-$ and nitric oxide (NO) production, lysozyme activity, and the proinflammatory cytokine gene expression of $IL-1{\beta}$ and $TNF-{\alpha}$ in olive flounder significantly in vivo, whereas non-CpG-ODNs did not produce these effects or produced them to a lesser extent. This implied that CpG-ODNs could stimulate cellular and humoral immunity and cytokine gene expression in olive flounder. This is the first evidence of NO production and the first study on the mRNA expression of the proinflammatory cytokine genes $IL-1{\beta}$ and $TNF-{\alpha}$ in olive flounder in response to CpG-ODNs. Comparison of the variation in NO production and lysozyme activity to that of other studies led us to postulate that a group-specific difference exists in the immune responses of olive flounder against CpG-ODNs. Furthermore, the detailed immunostimulatory spectrum of CpG-ODNs in olive flounder could be a useful index with which to analyze the effect of CpG-ODNs against the challenge test prior to field applications.

• Tuberculosis and Respiratory Diseases
• /
• 제45권3호
• /
• pp.553-564
• /
• 1998

연구배경: LPS에 대한 숙주의 초기반응은 proin-flammatory cytokines의 분비이다. 이러한 "초기 반응" cytokines는 인지세포에서 표적세포 등에 신호를 전달하여 다른 대식세포를 포함한 면역세포, 폐장내 간엽성 세포들을 자극하여 화학주성인자, 성장인자, 유착분자 등의 발현을 증폭시키게 되면서 전염증단계가 정열하게된다. 내독소유발 급성폐손상에서 폐장내 proinflammatory cytokine 기원 세포들은 활성화된 대식세포/단핵구 외에 폐조직으로 유입된 동원 호중구의 역할이 중요하게 인식되고 있으며 이외에도 간엽성 세포들에서도 발현되고 있는 것으로 밝혀지고 있다. 저자들은 실험 백서에서 내독소를 정백내 주입하여 유발시킨 급성폐손상에서 proinflammatory cytokines인 TNF-$\alpha$ 및 IL 6 기원의 주된 세포(들)를 규명해 보고자 하였다. 방 법: 체중 $250{\pm}50g$의 건강체인 웅성 Sparague-Dawley를 정상 대조군(Normal Control Saline Group)과 내독소유발 급성폐손상군으로 분류하였으며 급성폐손상군은 백혈구결핍 내독소군(CPA-ETX Group)과 대조-내독소군(ETX Group)으로 하였다. 실험백서를 phenthotal sodium으로 마취한 후 생리식염수 0.4ml(control) 혹은 동량의 생리식염수에 용해시킨 LPS (055 : B5 E. coli, Sigma Chemical Co., St. Louis, MO), 5mg/kg를 백서 미부정맥으로 주사한 후 각각 0 및 3, 6 시간에 회생시켰다. 백혈구결핍 내독소군은 cyclophophamide, 7mg/kg를 복강내 주입하여 5 일째에 LPS를 같은 방법으로 주입하여 3, 6시간에 각각 희생시켰다. 각군에서 기관지폐포세척술을 전술한 바와 같이 시행하여 총백혈구수, 분획세포수 및 총단백량을 산출하였고 기관지폐포세척 TNF-$\alpha$ 및 IL 6를 생물학적 방법으로 각각 측정하여 비교하였다. 동시에 기관지폐포세척술을 하지 않은 정상대조군 및 대조-내독소군에서 TNF-$\alpha$ 및 IL 6 단백에 대한 면역조직화학염색을 시행하였다. 결 과: 기관지폐포세척 세포 및 단백량 측정 결과 정상대조군에 비해 대조-내독소군에서 기관지폐포세척 총백혈구수는 3, 6 시간째에 각각 유의한 증가를 보였으나 (p<0.01), 백혈구결핍 내독소군과는 차이가 없었다. 대조-내독소군은 정상대조군에 비해 기관지폐포세척단핵구 및 호중구수가 3, 6 시간째에 각각 유의하게 증가하였으며 (p<0.05) 특히 호중구 분획율의 유의한 증가를 동반하였다(p<0.05). 백혈구결핍 내독소군은 정상대조군에 비해 3, 6시간째에 각각 기관지폐포세척 호중구수 및 호중구분획율의 유의한 감소를 보였으나 (p<0.05) 기관지폐포세척 단핵구수 및 단핵구 분획율에서는 양군간에 차이가 없었다. 기관지폐포세척 총단백량은 내독소군에서 3, 6시간째에 각각 정상대조군에 비해 유의한 증가를 보였으며(p<0.05) 내독소군간에는 6시간째에 대조-내독소군에서 백혈구결핍 내독소군에 비해 유의하게 높았다(p<0.05). 기관지폐포세척 TNF-$\alpha$ 및 IL-6의 농도는 정상대조군에서 각각 $0.06{\pm}0.06$ U/ml(n=5) 및 $0.45{\pm}0.23$ U/ml(n=5)이었다. 내독소군에서 TNF-$\alpha$와 IL-6는 정상대조군에 비해 유의하게 상승되었으며 (p<0.05), 백혈구결핍 내독소군과 대조-내독소군간에 차이는 없었다. 면역조직화학염색결과 내독소 정맥 주입 3시간 및 6시간후의 폐조직에서 TNF-$\alpha$ 및 IL-6 단백이 폐포대식세포와 간질대식세포들에서 강하게 염색되는 소견을 관찰할 수 있었다. 결 론: 내독소혈증 유발 급성 폐손상의 초기 손상에 중요한 역할을 하는 proinflammatory cytokine의 주된 기원세포는 활성화된 폐포대식세포/단핵구세포들일 것으로 사료되며 이들 세포가 내독소혈증 유발 급성폐손상 발생에 주도적인 역할을 할 것으로 사료되었다.