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한국인 궤양성 대장염 환자의 말초혈액에서 CCL20 유전자의 발현 및 sulphasalazine과 glucocorticoid에 의한 조절작용
최석채(Suck Chei Choi),나용호(Yong Ho Nah),정연태(Yeun Tai Chung),한원철(Won Cheol Han),이명수(Myeung Su Lee),전창덕(Chang-Duk Jun) 대한해부학회 2004 Anatomy & Cell Biology Vol.37 No.6
염증성 장 질환 (inflammatory bowel disease; IBD)은 만성적인 염증으로 궤양성 대장염 (ulcerative colitis)과 크론씨 병(Crohn,s disease)으로 분류되어진다. 최근 혈액의 단핵구 세포와 장 상피세포에서 발현되어지는 Nod2 유전자가 크론씨 병의 원인 유전자로 알려지면서 혈액의 단핵구 세포가 염증성 장 질환에 중요한 역할을 수행할 수 있을 것으로 재조명되었다. 본 연구는 Nod2 유전자처럼 단핵구 세포와 장 상피세포에서 공통으로 발현하며, 인체에서 선천성 면역능과 후천성 면역능을 연결하는 것으로 알려진 CCL20 유전자가 한국인에서 발병율이 높은 궤양성 대장염에서 어떻게 발현이 조절되는지 알아본 것이다. CCL20 유전자는 정상인에 비하여 대부분의 궤양성 대장염 환자의 혈액 단핵구 세포 및 장 상피조직에서 발현이 증가되어져 있었다. 본 연구에 참여한 환자의 disease activity index (DAI)와 CCL20 유전자 발현의 상관관계를 구한 결과 흥미롭게도 CCL20가 높게 발현된 환자들은 대다수 이전에 약물치료를 받지 않은 것으로 나타났다. 이러한 결과는 CCL20 유전자가 초기 궤양성 대장염의 발병에 관여하고 있으며 항-염증제 치료에 반응을 하는 유전자라는 것을 암시하는 결과이다. 이를 증명하기 위하여 이전에 항-염증치료를 받지 않은 궤양성 대장염 환자에 대하여 3개월 간 5-amino salicylic acid (5-ASA)와 glucocorticoid 유도체인 dexamethasone (DEX)으로 약물치료를 수행하였다. 이 결과 CCL20 유전자의 발현이 이들 약물치료를 받은 환자에서 급격히 감소하였음을 알 수 있었다. 이를 세포수준에서 확인하기 위하여 THP-1 단구세포와 HT-29 장 상피세포에 TNF-α 또는 IL-1β로 CCL20를 유도한 다음 5-ASA와 DEX를 처리한 결과 환자에서와 같은 효과를 검정할 수 있었다. 이러한 결과는 CCL20가 궤양성 대장염 환자에서 혈액 및 장 조직의 면역학적 병리작용에 중요하게 관여하고 있으며 궤양성 대장염의 진단 및 예후 판정에 도움을 줄 수 있음을 시사한다. Discovery of Nod2 has brought to light the significance of mononuclear cells as well as epithelial cells in inflammatory bowel disease (IBD) pathogenesis. Similarly, CCL20 is expressed in both mononuclear cells and epithelial cells and is likely to link innate and acquired immunity. We therefore asked whether CCL20 expression is altered in the peripheral blood mononuclear cells (PBMCs) from patients with ulcerative colitis (UC), a major type of IBD in Korea, and is correlated with the disease activity. The expression levels of CCL20 mRNA were significantly high in the PBMCs from the patients with UC. CCL20 protein expression was also up-regulated in the mucosal epithelium in UC but not in normal controls. Interestingly, however, disease activity index (DAI) revealed that untreated UC groups express higher expression levels of CCL20 mRNA than treated UC groups, implying that CCL20 may be a potential target for the anti-inflammatory treatments. In an agreement with this, three months follow up study revealed that the UC patients who were treated with 5-amino salicylic acid (5-ASA) and glucocorticoid showed dramatic decrease in their CCL20 mRNA levels as compared to untreated ones. Moreover, TNF-α- or IL-1β-induced CCL20 secretion in human epithelial HT-29 cells was significantly diminished by the treatment with 5-ASA and/or dexamethasone, suggesting that CCL20 may be one of the central targets of the anti-inflammatory drugs. Collectively, these results suggest that CCL20 expression in UC may be associated with altered immune and inflammatory responses in the blood as well as the intestinal mucosa and further implied a potential for CCL20 as an important diagnostic marker for UC.
Sun- Kyung Lee,Sung-Hee Pi,Sung -Hyun Kim,Kyung-San Min,Hwa-Jeong Lee,Hoon -Sang Chang,Kyung-Hwa Kang,Hyung-Ryong Kim,Hong-In Shin,Suk-Keun Lee,Eun-Cheol Kim 대한구강악안면병리학회 2007 대한구강악안면병리학회지 Vol.31 No.5
Although substance P (SP). a potent pro-inflammatory peptide, is involved in inflammation and immune responses, the effect of SP 011 the expression of macl'ophage inJlammatol'Y protein 3a (MIP-3a. CCL20) in periodontal ligament (PDL) cells a l'e unknown Equally as enigmatic is the link between SP. the stress protein heme oxygenase-l (HO-l) , and CCL20 product ion. We investigated whether SP induces the release of chemokine CCL20 from irrunortalized POL (IPDL) cells. and further claif’y SP mediated pathways . We also exarnined the relationship between HO-l and CCL20 by treating POL cells with SP Incubating IPOL cells with SP incl'eased ex pl'ession of CCL20 mRNA and CCL20 protein in a dose-time dependent manner. Highly selective p38 and ERKl/2 inhibitors abl'ogated SP-induced expression of CCL20 lD IPOL cells SP is also responsible fo l' ini tiating phosphorylation of I/( B‘ degl'adation of IK B. and activation of NF-/( B. SP induced expression of HO-l in both a concentration- and time-dependent manner. and CCL20 refl ected similal' patterns. The inductive effects of SP on HO-l and CCL20 were enhanced by HO- l inducer hemin and the membrane-permea ble cGMP analog 8-bromo-cGMP Conversely, this pathway was inhi bited by the HO-l inhibitor zinc Pl'otoporphyrin IX (ZnPP IX) and the selective inhibitor of guanylate cyclase‘ 1H- [1. 2. 4]uxad iazole[4, 3-alquinoxal i n- 1-one (ODQ) We report hel'ein the pathway that connects SP a long with other modulators 0 1' neuroimmunoregulationto the induction of HO-1 and the inflanunatol'y mediatol' MIP- 3a /CCL20 in IPDL cel ls. which play an impol'tant role in the development 0 1' pe- I'iodontitis or inflammation during ol'thodontic tooth movement
Kim, Kyung Eun,Houh, Younkyung,Park, Hyun Jeong,Cho, Daeho MDPI 2016 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.17 No.2
<P>Psoriasis is a common skin disease accompanied by chronic inflammation. In previous studies, erythroid differentiation regulator 1 (ERDR1) was shown to have a negative correlation with proinflammatory cytokine IL-18. However, the role of ERDR1 in the inflammatory skin disease psoriasis has not been evaluated. In this study, to investigate the role of ERDR1 in psoriasis, recombinant ERDR1 was injected intraperitoneally into a psoriasis mouse model. Recombinant ERDR1 (rERDR1) significantly alleviated the symptoms of psoriasis-like skin inflammation and reduced the mRNA of various psoriasis-related markers, including keratin 14, S100A8, and Th17-related cytokines IL-17 and IL-22, suggesting that rERDR1 exerts therapeutic effects on psoriasis via the regulation of Th17 functions. Additionally, the expression of CCL20, a well-known Th17 attracting chemokine, was determined. CCL20 expression significantly decreased in the rERDR1-injected group compared with the vehicle (PBS)-injected group. CCR6 expression in the psoriatic lesional skin was also decreased by rERDR1 administration, implying the inhibition of CCR6-expressing Th17 cell chemotaxis via the downregulation of CCL20. Taken together, this study provides the first evidence that ERDR1 may be a potential therapeutic target for psoriasis.</P>
김민영,최유원,황형서 한국생물공학회 2021 Biotechnology and Bioprocess Engineering Vol.26 No.3
Mevastatin (HMG-CoA reductase inhibitor) isolated from Penicillium citrinum is known to the first statin that inhibitor of cholesterol synthesis. Recently, several clinical reports of other statins suggest its role on reducing the severity of psoriasis, but the available evidence on cellular/molecular level of mevastatin is unclear. Thus, this study was to determine the molecular/cellular mechanism of mevastatin using TNF-α/IL-17A stimulated HaCaT cells. First, the safety and effectiveness of mevastatin were confirmed through the comparative experiment of five statin derivatives. Mevastatin decreased mRNA levels of cytokines (IL-1α/β, IL-6, and IL-8), chemokine (CC motif) ligand 20 (CCL20), and keratin proteins (Keratin 5/14/6/ 16) known to be overexpressed in psoriasis. In addition, mevastatin significantly reduced phosphorylation of NF- κB, MAPKs and STAT3 in TNF-α/IL-17 signaling pathway. Moreover, mevastatin specifically suppressed keratin 5/14 proteins expressed in the keratinocyte differentiation process of the basal layer and keratin 6A/16 overexpressed in patients with psoriasis. These results imply that mevastatin not only can inhibit psoriasis-induced inflammatory cytokines and chemokines, but also can suppress psoriasisrelated keratin proteins.
Nguyen, Ly Thi Huong,Ahn, Sang-Hyun,Nguyen, Uy Thai,Yang, In-Jun Elsevier 2018 Phytomedicine Vol.47 No.-
<P><B>Abstract</B></P> <P><B>Background</B></P> <P>The traditional herbal formula, Dang-Gui-Liu-Huang Tang (DGLHT) has been previously shown to inhibit T lymphocyte proliferation and suppress dendritic cell function. Hypothesis/Purpose: To assess the therapeutic value of DGLHT for the treatment of psoriasis, a Th1 and/or Th17 cell-mediated inflammatory skin disease, and to investigate the underlying molecular mechanisms.</P> <P><B>Methods</B></P> <P>An <I>in vivo</I> mouse model of imiquimod (IMQ)-induced psoriasis-like inflammation was used to investigate the effect of DGLHT. The anti-inflammatory effects of an ethanolic extract of DGLHT (DGLHT-E) and the mechanism responsible were examined in an <I>in vitro</I> model using IL-1α, IL-17A, IL-22, oncostatin M, plus TNF-α (M5) stimulated HaCaT cells. The anti-proliferative effect of DGLHT-E was examined by analyzing the expression levels of K16, K17 and Ki67 in IL-22 stimulated HaCaT cells. <I>Results:</I> Topical application of 1% DGLHT-E significantly reduced psoriasis-like symptoms including scaling and epidermal hyperplasia in IMQ-treated mice. Immunohistochemical studies showed that DGLHT-E exerted potent anti-inflammatory effects by inhibiting IL-22 production in local skin lesions. DGLHT-E also attenuated the productions of CXCL10 and CCL20 in M5-stimulated HaCaT cells by suppressing the ERK1/2, JNK and STAT3 signaling pathways. Furthermore, berberine hydrochloride, a primary constituent of DGLHT-E inhibited the expressions of the proliferation markers K16 and K17 in IL-22 stimulated HaCaT cells.</P> <P><B>Conclusion</B></P> <P>These results suggested that DGLHT-E offers a possible treatment for psoriasis, and that berberine hydrochloride might be a useful component of ointment-based treatments for psoriatic lesions.</P> <P><B>Graphical <B>abstract</B> </B></P> <P>[DISPLAY OMISSION]</P>