• Bulletin of the Korean Chemical Society
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• 제31권12호
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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.

• 대한본초학회지
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• 제22권4호
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• pp.109-116
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• 2007

Objectives : In the present study, we investigated anti-inflammatory effects of chloroform fraction of Coptidis rhizoma (CR-C) on the production of inflammatory mediators such as nitric oxide (NO) and proinflammatory cytokines, tumor necrosis factor-alpha (TNF-${\alpha}$) and interleukin-1beta (IL-1${\beta}$) in LPS-stimulated BV2 microglial cells. Methods : Copriditis rhizoma was extracted with 80% methanol, and then extracted with chloroform. BV2 cells were pre-treated with CR-C, and stimulated with LPS. The cytotoxicity was determined by MTT assay. The production of NO and cytokines was measured by Griess assay and ELISA. The mRNA expression of inducible nirtic oxide synthase (iNOS) and cytokines were determined by RT-PCR. Results : CR-C significantly inhibited the production of NO. TNF-${\alpha}$ and IL-1${\beta}$ in a dose-dependent manner in LPS-stimulated BV2 cells. In addition, CR-C suppressed the mRNA expressions of iNOS and inflammatory cytokines induced by LPS stimulation. These results indicate that CR-C was involved in anti-inflammatory effects in activated microglia. Conclusion : The present study suggests that chloroform extract of Coptidis rhizoma can be useful as a potential anti-inflammatory agent for treatment of various neurodegenerative diseases.

• Journal of Ginseng Research
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• 제28권2호
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• pp.120-126
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• 2004

수천 년 동안 전통적 약제로 사용되어온 고려인삼은 중추신경계의 항상성을 유지하고 면역기능을 강화하는 효능을 나타내는 것으로 알려져 있다. 신경계질환의 진행이 대부분 염증 또는 면역반응을 수반하며, 이로 인하여 손상된 신경세포의 수복과정에 교세포 기원의 매개물질들이 기여하므로, 교세포에서의 cytokine 및 NO생성에 대한 연구는 신경기능과 신경면역기능의 조절 뿐 아니라 신경계 질환에 대한 연구의 초석이라고 할 수 있다. 따라서 본 연구에서는 고려인삼의 신경면역 및 염증반응 조절효과에 대하여 연구하고자 하였으며, 이를 위하여 흰쥐 대뇌피질의 교세포를 일차배양하며 고려인삼사포닌 분획을 처치하여 TNF-$\alpha$, IL-1$\beta$, 및 NO의 생성변동을 연구하였다. 백삼 사포닌은 50-500$\mu\textrm{g}$/ml 용량에서 TNF-$\alpha$와 IL-1$\beta$ 생성을 증가시켰으며, 미세교세포에서 iNOS 발현 및 NO생성을 유도하였고 성상세포의 stellation을 초래하였다. 특히 백삼사포닌 50-100 $\mu\textrm{g}$/ml는 세포독성을 거의 나타내지 않았으므로 이들 용량에 의한 교세포의 적절한 활성화가 중추신경계 면역기능 증가 및 염증반응 조절에 기여할 것으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.307-314
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• 2015

Background: Bladder cancer is among the five most common malignancies worldwide. Altered expression of suppressor of cytokine signaling -3 (SOCS-3) has been implicated in various types of human cancers; however, its role in bladder cancer is not well established. Aim: The present study was undertaken to investigate the mRNA expression of SOCS-3 in normal and cancerous bladder tissue and to explore its correlation with urinary levels of some proinflammatory cytokines, cytokeratin-18 (CK -18) and with tumor histopathological grading, in order to evaluate their role as potential diagnostic markers. Materials and Methods: SOCS3 mRNA expression levels were evaluated using quantitative real time PCR. Urinary levels of interleukins 6 and 8 were estimated by enzyme linked immunosorbent assay (ELISA). Cytokeratin-18 expression was analyzed by immuunohistochemistry then validated by ELISA. Results: SOC3 m RNA expression levels were significantly lower in high grade urothelial carcinoma ($0.36{\pm}0.12$) compared to low grade carcinoma ($1.22{\pm}0.38$) and controls ($4.08{\pm}0.88$), (p<0.001). However, in high grade urothelial carcinoma the urinary levels of IL-6, IL-8, total CK-18($221.33{\pm}22.84pg/ml$, $325.2{\pm}53.6pg/ml$, $466.7{\pm}57.40U/L$ respectively) were significantly higher than their levels in low grade carcinoma ($58.6{\pm}18.6pg/ml$, $58.3{\pm}50.2pg/ml$, $185.5{\pm}60.3U/L$ respectively) and controls ($50.9{\pm}23.0pg/ml$, $7.12{\pm}2.74pg/ml$, $106.7{\pm}47.3U/L$ respectively), (p<0.001). Conclusions: Advanced grade of urothelial bladder carcinoma is significantly associated with lowered mRNA expression of SOC3 as well as elevated urinary levels of proinflammatory cytokines and CK-18. Furthermore, our results suggested that urinary IL-8, IL-6 and CK-18 may benefit as noninvasive biomarkers for early detection as well as histopathological subtyping of urothelial carcinoma.

• Journal of Nutrition and Health
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• 제49권6호
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• pp.429-436
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• 2016

본 연구에서는 피부의 표피와 진피에 분포하는 HaCaT 세포와 HDF 세포를 이용하여 항산화효과가 우수한 두릅순 추출물의 처리가 UVB에 의한 피부광노화를 억제할 수 있는지 알아보기 위하여 피부 염증반응과 관련한 사이토카인과 피부의 주요 구성 단백질인 collagen에 영향을 미칠 수 있는 MMP-1, type-I procollagen, TRPV-1 등의 단백질 발현에 미치는 영향을 분석하였다. HaCaT에 두릅순 추출물을 24시간 전처리한 경우 UVB ($55 mJ/cm^2$) 노출로 인해 증가한 염증매개인자인 IL-6, IL-8, $PGE_2$를 유의하게 감소시켰다. 또한, 피부 collagen의 정상적인 구조 및 양에 영향을 미치는 단백질들의 발현을 측정한 결과 HaCaT에서는 UVB 조사로 인해 증가한 TRPV-1과 MMP-1 단백질의 발현이 두릅순 에탄올 추출물의 전처리로 모두 감소하였고, HDF에서는 UVB를 조사한 대조군에 비하여 두릅순 추출물 처리가 MMP-1 단백질 발현을 감소시키는 동시에 collagen의 전구체인 type-I procollagen의 발현을 증가시키는 효과를 보였다. 이들 결과들로부터 항산화효과가 우수한 두릅순 70% 에탄올 추출물은 피부세포에서 UVB에 의한 염증반응을 억제시키는 동시에 피부 collagen의 감소를 억제시킴으로써 피부 광노화를 예방할 수 있는 천연 소재로 이용될 수 있다고 본다.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2019년도 추계학술대회
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• pp.92-92
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• 2019

Excessive or chronic inflammation contributes to the pathogenesis of many inflammatory diseases such as sepsis, rheumatoid arthritis, and ulcerative colitis. Hibiscus syriacus L. has been used as a medicinal plant in many Asian countries, even though its anti-inflammatory activity has been unclear. Therefore, we investigated the anti-inflammatory effect of anthocyanin fractions from the H. syriacus L. varieties Pulsae (PS) on the lipopolysaccharide (LPS)-induced expression of proinflammatory mediators and cytokines in RAW264.7 macrophages. PS suppressed LPS-induced nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) secretion concomitant with downregulation of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Furthermore, PS inhibited the production of proinflammatory cytokines such as tumor necrosis factor-alpha ($TNF-{\alpha}$), interleukin-6 (IL-6), and IL-12 in LPS-stimulated RAW264.7 macrophages. Further study showed that PS significantly decreased LPS-induced nuclear translocation of the nuclear $factor-{\kappa}B$ ($NF-{\kappa}B$) subunits, p65 and p50. Molecular docking data showed that many anthocyanins from PS fit into the hydrophobic pocket of MD2 and bound to Toll-like receptor 4 (TLR4), indicating that PS inhibits the TLR4-MD2-mediated inflammatory signaling pathway. Especially, apigenin-7-O-glucoside most powerfully bound to MD2 and TLR4 through LYS122, LYS122, and SER127 at a distance of $2.205{\AA}$, $3.098{\AA}$, and $2.844{\AA}$ and SER441 at a distance of $2.873{\AA}$ (docking score: -8.4) through hydrogen bonding, respectively. Additionally, PS inhibited LPS-induced TLR4 dimerization/expression on the cell surface, which consequently decreased MyD88 recruitment and IRAK4 phosphorylation. PS completely blocked LPS-mediated mortality in zebrafish larvae by diminishing the recruitment of neutrophil and macrophages accompanied by low levels of proinflammatory cytokines. Taken together, our results indicate that PS attenuates LPS-mediated inflammation in both in vitro and in vivo by blocking the TLR4/MD2-MyD88/IRAK4-$NF-{\kappa}B$ axis. Therefore, PS might be used as a novel modulatory candidate for effective treatment of LPS-mediated inflammatory diseases.

• Archives of Pharmacal Research
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• 제25권6호
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• pp.910-916
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• 2002

Endotoxin tolerance reduces the capacity of monocytes to produce proinflammatory cytokines, results in cellular immune paralysis, and down-regulates the production of helper T (Th)1 type cytokines with a shift toward a Th2 cytokine response. Prostaglandin (PG)E$_2$ in the immune system also results in macrophage inactivation and the suppression of Th1 activation and the enhancement of Th2 activation. However, the inhibitory effects of PGE$_2$ on the altered polarization of the Th cell and macrophage interleukin (IL)-6 production characterized in part by cellular immune paralysis in a state of endotoxin tolerance is unclear. This study was undertaken, using indomethacin, to investigate the role of endogenous PGE$_2$ on the Th cytokines and macrophage IL-6 production in a state of endotoxin tolerance compared to those with endotoxemia mice, wherein, in this latter case, the increased production of proinflammatory cytokines and PGE$_2$ is exhibited. Endotoxemia was induced by injection of lipopolysaccharide (LPS; 10 mg/kg in saline) i.p. once in BALB/c mice, and endotoxin tolerance was induced by pretreatment with LPS (1 mg/kg in saline) injected i.p. daily for two consecutive days and then with LPS 10 mg/kg on day 4. Splenocytes or macrophages were obtained from endotoxemia and endotoxin tolerance models pretreated with indomethacin, and then cytokine production was induced by Con A-stimulated splenocytes for the Th cytokine assays and LPS-stimulated macrophages for the IL-6 assay. Our results showed that endotoxemia led to significantly reduced IL-2 and IL-4 production, to significantly increased IL-6 production, whereas interferon $(IFN)-{\gamma}$ production was not affected. Indomethacin in the case of endotoxemia markedly attenuated $IFN-{\gamma}$ and IL-6 production and didnt reverse IL-2 and IL-4 production. Endotoxin tolerance resulted in the significantly reduced production of IL-2 and $IFN-{\gamma}$ and the significantly increased production of IL-4 and IL-6. Indomethacin in endotoxin tolerance greatly augmented IL-2 production, significantly decreased IL-4 production, and slightly attenuated IL-6 production. These findings indicate that endogenous PGE$_2$ may mediate the suppressed Th1 type immune response, with a shift toward a Th2 cytokine response in a state of endotoxin tolerance, whereas endotoxemia may be regulated differentially. Also, endogenous PGE$_2$ may mediate macrophage IL-6 production in the case of endotoxemia to a greater extent than in the case of endotoxin tolerance.

• Parasites, Hosts and Diseases
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• 제47권3호
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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.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2002년도 Current Trends in Toxicological Sciences
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• pp.103-104
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• 2002

Cyclooxygenase (COX), an important enzyme involved in mediating the inflammation, catalyzes the rate-limiting step in the formation of prostaglandins from arachidonic acid. There are two isoforms of COX, designated as COX-1 and COX-2. While COX-1 is constitutively expressed in most tissues, COX-2 can be induced transiently by proinflammatory cytokines, endotoxins, growth factors, oncogenes, UV and mitogens.(omitted)

• 한국독성학회:학술대회논문집
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• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
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• pp.154-155
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• 2001

Cyclooxygenase-2 (COX-2) is an inducible enzyme expressed in response to a variety of proinflammatory agents and cytokines. COX-2 expression has been shown to be elevated in several different types of human cancer. The presence of oncogenic ras has been associated with constitutive induction of COX-2 in certain H-ras transformed cells, and COX-2 overexpression confers resistance to apoptosis.(omitted)