• Title, Summary, Keyword: proinflammatory cytokine

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Generation of Antagonistic RNA Aptamers Specific to Proinflammatory Cytokine Interleukin-32

  • Kim, Se-Ho;Kim, Jung-Hee;Yoon, Su-Jin;Kim, Keun-Sik;Yoon, Moon-Young;Yoon, Do-Young;Kim, Dong-Eun
    • Bulletin of the Korean Chemical Society
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    • v.31 no.12
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    • pp.3561-3566
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    • 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.

Cytokine Gene Expression of Peritoneal Tissues in Response to Mixed Infection of Bacteroides fragilis and Escherichia coli (Bacteroides fragilis와 대장균의 혼합 감염에 의한 복강 조직의 Proinflammatory Cytokine 유전자 발현 조절)

  • Kim, Jung-Mogg;Kim, Young-Jeon;Park, Hwon-Kyum;Cho, Yang-Ja
    • The Journal of the Korean Society for Microbiology
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    • v.35 no.1
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    • pp.41-48
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    • 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.

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Effect of Baicalin on the Ex vivo Production of Cytokines in Pristane-Induced Lupus Mice (프리스탄 유도한 루푸스 생쥐에서 사이토카인 Ex vivo 생산에 미치는 Baicalin의 효과)

  • Chae, Byeong Suk
    • YAKHAK HOEJI
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    • v.60 no.1
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    • pp.21-28
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    • 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.

Activating transcription factor-3 induction is involved in the anti-inflammatory action of berberine in RAW264.7 murine macrophages

  • Bae, Young-An;Cheon, Hyae Gyeong
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.4
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    • pp.415-424
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    • 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.

Proinflammatory Cytokine and Nitric Oxide Production by Human Macrophages Stimulated with Trichomonas vaginalis

  • Han, Ik-Hwan;Goo, Sung-Young;Park, Soon-Jung;Hwang, Se-Jin;Kim, Yong-Seok;Yang, Michael Sungwoo;Ahn, Myoung-Hee;Ryu, Jae-Sook
    • The Korean Journal of Parasitology
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    • v.47 no.3
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    • pp.205-212
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    • 2009
  • Trichomonas vaginalis commonly causes vaginitis and perhaps cervicitis in women and urethritis in men and women. Macrophages are important immune cells in response to T. vaginalis infection. In this study, we investigated whether human macrophages could be involved in inflammation induced by T. vaginalis. Human monocyte-derived macrophages (HMDM) were co-cultured with T. vaginalis. Live, opsonized-live trichomonads, and T. vaginalis Iysates increased proinflammatory cytokines, such as TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 by HMDM. The involvement of nuclear factor (NF)-${\kappa}B$ signaling pathway in cytokine production induced by T. vaginalis was confirmed by phosphorylation and nuclear translocation of p65 NF-${\kappa}B$. In addition, stimulation with live T. vaginalis induced marked augmentation of nitric oxide (NO) production and expression of inducible NO synthase (iNOS) levels in HMDM. However, trichomonad-induced NF-${\kappa}B$ activation and TNF-${\alpha}$ production in macrophages were significantly inhibited by inhibition of iNOS levels with L-NMMA (NO synthase inhibitor). Moreover, pretreatment with NF-${\kappa}B$ inhibitors (PDTC or Bay11-7082) caused human macrophages to produce less TNF-${\alpha}$. These results suggest that T. vaginalis stimulates human macrophages to produce proinflammatory cytokines, such as IL-1, IL-6, and TNF-${\alpha}$, and NO. In particular, we showed that T. vaginalis induced TNF-${\alpha}$ production in macrophages through NO-dependent activation of NF-${\kappa}B$, which might be closely involved in inflammation caused by T. vaginalis.

Regulatory Effect of Fresh Rehmanniae Radix Extract on the in Vitro Production of Proinflammatory Cytokines in Pristane-Induced Lupus Mice

  • Chae, Byeong-Suk;Yang, Jae-Heon
    • Natural Product Sciences
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    • v.13 no.4
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    • pp.322-327
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    • 2007
  • Fresh Rehmanniae radix is known as a traditional medicine with anti-inflammatory and antioxidant activities. However, whether Rehmanniae radix attenuates autoimmune inflammation in lupus models characterized by T cell-dependent autoimmune disease including overproduction of proinflammatory cytokines, loss of T cell tolerance, and B cell hyperactivity remains unclear. We investigated the effect of fresh Rehmanniae radix methanol extracts (RGMeOH) on the in vitro overproduction of proinflammatory cytokines by immune cells from pristaneinduced lupus BALB/c mice. These results showed that RGMeOH remarkably attenuated Con A-increased overproduction of proinflammatory cytokines, such as IL-2, IFN-${\gamma}$, IL-6 and IL-10 by splenocytes from pristaneinduced lupus mice. RGMeOH greatly reduced LPS-induced production of TNF-${\alpha}$ by splenic macrophages from pristane-induced lupus mice, while significantly enhanced LPS-induced production of IL-10 but did not alter IL-6 by splenic macrophages and splenocytes. These findings suggest that RGMeOH may ameliorate lupus systemic inflammatory autoimmunity via down-regulation of TNF-${\alpha}$ and T cell-dependent cytokine production.

Inhibition of Proinflammatory Cytokine-induced Invasiveness of HT-29 Cells by Chitosan Oligosaccharide

  • Nam, Kyung-Soo;Kim, Mee-Kyung;Shon, Yun-Hee
    • Journal of Microbiology and Biotechnology
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    • v.17 no.12
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    • pp.2042-2045
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    • 2007
  • The effect of chitosan oligosaccharide (COS, 1 kDa${\gamma}$, 10 ng/ml IL-$1{\alpha}$, and 25 ng/ml TNF-${\alpha}$) in HT-29 cells. Inducible nitric oxide synthase (iNOS) expression induced by these cytokines was inhibited by COS. COS pretreatment inhibited the invasiveness of cytokines-treated HT-29 cells through Matrigel-coated membrane in a dose-dependent manner. COS also inhibited cytokines-induced matrix metalloproteinase (MMP)-2 activity. This study shows that proinflammatory cytokines induce NO production, iNOS expression, and invasiveness of human colorectal adenocarcinoma HT-29 cells. COS pretreatment inhibited cytokines-mediated NO production, iNOS expression, and invasiveness of HT-29 cells. These results provide sufficient information for the further development of COS as an antitumor metastatic agent for the treatment of colon cancer.

Efficacy of Oral Korean Red-ginseng on sCRP and Soreness after Muscle Damage

  • NA, Hyun-Jong
    • The Journal of Korean Medicine
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    • v.26 no.4
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    • pp.39-45
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    • 2005
  • Objectives: The study investigated the efficacy of oral Korean red-ginseng (RG) on sCRP response mediated by eccentric contraction-induced muscle damage and discussed its mechanism. Methods: Nineteen healthy young subjects (aged 24.4$\pm$2.07 yr) volunteered for this double blind test. They were classified into either the RG group (N=10) or placebo (P) group (N=9) during the 10-d experimental protocol. Blood samples were collected on T1 (baseline), T1 (1h), T2 (1d), T3 (2d) and T4 (3d) after eccentric contraction-induced injury on the seventh day. Statistical analyses were conducted using nonparametric methods (p<0.05). Results: The RG group increased sCRP more than P group and didn't increase soreness peak at T2, not significant. There were no correlations between soreness intensity and sCRP. Oral RG had little efficacy for reducing sCRP at the muscle damage-mediated acute phase; rather, it increased because of its proinflammatory cytokine production. Conclusions: Oral RG could stimulate proinflammatory cytokine production, and occasionally bal-pyo-beob could be helpful for the efficient recovery of muscle injury.

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Proteinase 3-processed form of the recombinant IL-32 separate domain

  • Kim, Sun-Jong;Lee, Si-Young;Her, Erk;Bae, Su-Young;Choi, Ji-Da;Hong, Jae-Woo;JaeKal, Jun;Yoon, Do-Young;Azam, Tania;Dinarello, Charles A.;Kim, Soo-Hyun
    • BMB Reports
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    • v.41 no.11
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    • pp.814-819
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    • 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.

Effects of High-Protein Diet and/or Resveratrol Supplementation on the Immune Response of Irradiated Rats

  • Kim, Kyoung Ok;Park, Hyunjin;Kim, Hyun-Sook
    • Preventive Nutrition and Food Science
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    • v.19 no.3
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    • pp.156-163
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    • 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.