IL-1F5, -F6, -F8, and -F9: a novel IL-1 family signaling system that is active in psoriasis and promotes keratinocyte antimicrobial peptide expression.
IL-1F5, -F6, -F8, and -F9: a novel IL-1 family signaling system that is active in psoriasis and promotes keratinocyte antimicrobial peptide expression.
复制标题
DOI：
10.4049/jimmunol.1003162
复制
发表时间：
2011-02-15
期刊：
影响因子：
--
通讯作者：
Gudjonsson JE
中科院分区：
文献类型：
--
作者：
Johnston A;Xing X;Guzman AM;Riblett M;Loyd CM;Ward NL;Wohn C;Prens EP;Wang F;Maier LE;Kang S;Voorhees JJ;Elder JT;Gudjonsson JE
白细胞介素 -1F6、白细胞介素 -1F8、白细胞介素 -1F9以及白细胞介素 -1受体6（RP2）的受体拮抗剂白细胞介素 -1F5构成了一种新的白细胞介素 -1信号系统，其在皮肤中的特征尚不明确。为了进一步明确这些细胞因子在健康和发炎皮肤中的特征，我们使用实时定量聚合酶链反应（QRT - PCR）和免疫组织化学方法研究了它们在健康对照（NN）、未受累银屑病（PN）和银屑病斑块（PP）皮肤中的表达。与PN皮肤相比，PP皮肤中白细胞介素 -1F5、 -1F6、 -1F8和 -1F9的表达增加了2 - 3个数量级，免疫组织学结果也支持这一点。此外，用依那西普治疗银屑病导致白细胞介素 -1F5、 -1F6、 -1F8和 -1F9的信使核糖核酸（mRNA）显著降低，同时临床症状改善。在两种银屑病小鼠模型的受累皮肤中也观察到白细胞介素 -1F5、 -1F6、 -1F8和 -1F9表达的类似增加。白细胞介素 -1α和肿瘤坏死因子 -α可诱导正常人角质形成细胞表达白细胞介素 -1F5、 -1F6、 -1F8和 -1F9转录本，这表明它们在发炎的上皮细胞中具有重要作用。基因芯片分析显示，这些细胞因子可诱导重组人表皮中抗菌肽和基质金属蛋白酶的表达。特别是白细胞介素 -1F8可增加人β - 防御素2（HBD2）、人β - 防御素3（HBD3）和抗菌肽（CAMP）的信使核糖核酸表达以及人β - 防御素2和人β - 防御素3的蛋白质分泌。总之，我们的数据表明这些新型细胞因子在炎症性皮肤病中具有重要作用，并确定这些肽为银屑病治疗的潜在靶点。
IL-1F6, IL-1F8 and IL-1F9 and the IL-1R6(RP2) receptor antagonist IL-1F5 constitute a novel IL-1 signaling system that is poorly characterized in skin. To further characterize these cytokines in healthy and inflamed skin, we studied their expression in healthy control (NN), uninvolved psoriasis (PN) and psoriasis plaque (PP) skin using QRT-PCR and immunohistochemistry. Expression of IL-1F5, -1F6, -1F8, and -1F9 were increased 2-3 orders of magnitude in PP versus PN skin, which was supported immunohistologically. Moreover, treatment of psoriasis with etanercept led to significantly decreased IL-1F5, -1F6, -1F8 and -1F9 mRNAs, concomitant with clinical improvement. Similarly increased expression of IL-1F5, -1F6, -1F8 and -1F9 was seen in the involved skin of two mouse models of psoriasis. Suggestive of their importance in inflamed epithelia, IL-1α and TNF-α induced IL-1F5, -1F6, -1F8, and -1F9 transcript expression by normal human keratinocytes. Microarray analysis revealed that these cytokines induce the expression of anti-microbial peptides and matrix metalloproteins by reconstituted human epidermis. In particular, IL-1F8 increased mRNA expression of HBD2, HBD3 and CAMP and protein secretion of HBD2 and HBD3. Collectively, our data suggest important roles for these novel cytokines in inflammatory skin diseases and identify these peptides as potential targets for antipsoriatic therapies.
登录
查看更多内容
影响因子：
4.8
作者：
Kumar, S;McDonnell, PC;Young, PR
通讯作者：
Young, PR
影响因子：
6.5
作者：
MANSBRIDGE, JN;KNAPP, AM;STREFLING, AM
通讯作者：
STREFLING, AM
影响因子：
168.9
作者：
Mease, PJ;Goffe, BS;Burge, DJ
通讯作者：
Burge, DJ
影响因子：
4.4
作者：
Busfield, SJ;Comrack, CA;Pan, Y
通讯作者：
Pan, Y
影响因子：
4.8
作者：
Lin, HS;Ho, AS;Ford, JE
通讯作者：
Ford, JE