Functional effects of interleukin 31 in human primary keratinocytes
Functional effects of interleukin 31 in human primary keratinocytes
复制标题
DOI：
10.1111/j.1398-9995.2011.02545.x
复制
发表时间：
2011-07-01
期刊：
影响因子：
12.4
通讯作者：
Werfel, T.
中科院分区：
文献类型：
--
作者：
Kasraie, S.;Niebuhr, M.;Werfel, T.
背景：白细胞介素（IL）-31是一种T细胞因子，通过IL-31 RA和OSMR组成的异源二聚体受体发挥作用，表达于上皮细胞，包括角质形成细胞。IL-31在特应性皮炎（AD）中的主要功能是诱导皮肤瘙痒。IL-31在人原代角质形成细胞（HPKs）中的炎症作用仍然不清楚。我们研究了HPKs.Methods中IL-31受体的表达、调节以及IL-31的功能：分别用TLR-2配体（Pam 3Cys、脂磷壁酸和肽聚糖）或Th 1和Th 2相关细胞因子（IFN-γ和IL-4）刺激人原代角质形成细胞。然后在mRNA和蛋白水平上研究IL-31 R的表达和调节以及IL-31刺激的功能效应，并与AD患者的HPKs进行比较。结果：Pam 3Cys或IFN-γ可显著上调IL-31 RA和OSMR的表达。IL-31激活HPKs中STAT-3磷酸化，其在用Pam 3Cys或IFN-γ预激活后增强。IL-31在用Pam 3Cys或IFN-γ上调受体后增强CCL 2的分泌。然而，这是没有观察到在角质形成细胞从AD患者的TLR-2表达受损被发现。结论：总之，我们的研究结果显示IL-31在HPKs的功能作用，并提供了一个新的TLR-2配体和IL-31之间的联系，可能是失调的AD。IL-31的功能改变可能与湿疹中的皮肤炎症有关，其中已经描述了金黄色葡萄球菌的皮肤定植和TLR-2的失调。
P>Background:Interleukin (IL)-31 is a T-cell cytokine acting through a heterodimeric receptor composed of IL-31RA and OSMR which is expressed on epithelial cells including keratinocytes. A major function of IL-31 in atopic dermatitis (AD) is the induction of pruritus in the skin. Inflammatory effects of IL-31 in human primary keratinocytes (HPKs) still remain unclear. We investigated expression, regulation of the IL-31 receptor as well as functions of IL-31 in HPKs.Methods:Human primary keratinocytes were stimulated with TLR-2 ligands (Pam3Cys, lipoteichoic acid and peptidoglycan), or Th1 and Th2 associated cytokines (IFN-gamma and IL-4), respectively. IL-31R expression and regulation as well as functional effects of IL-31 stimulation were then investigated at both the mRNA and protein level and compared with HPKs from patients with AD. The STAT signalling pathway and TLR-2 expression were investigated using Western blot and Immunohistochemical stainings, respectively.Results:Pam3Cys or IFN-gamma significantly up-regulated IL-31RA and OSMR expression. IL-31 activated STAT-3 phosphorylation in HPKs which was augmented after preactivation with Pam3Cys or IFN-gamma. IL-31 enhanced the secretion of CCL2 after up-regulation of the receptor with Pam3Cys or IFN-gamma. However, this was not observed in keratinocytes from AD patients where an impaired TLR-2 expression was found.Conclusions:Together, our findings show a functional role of IL-31 in HPKs and provide a new link between TLR-2 ligands and IL-31 which might be dysregulated in AD. Altered function of IL-31 may have implications for cutaneous inflammation in eczema where skin colonization with Staphylococcus aureus and dysregulation of TLR-2 have been described.