期刊
ALLERGY
卷 66, 期 7, 页码 845-852出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1398-9995.2011.02545.x
关键词
atopic dermatitis; human primary keratinocytes; IFN-gamma; IL-31; IL-31R; Pam3Cys
资金
- Deutsche Forschungsgemeinschaft [(GRK) 1441/1, SFB 566, A6]
- [SFB 566]
- [GRK 1441]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据