Semaphorin 7A on keratinocytes induces interleukin-8 production by monocytes
Semaphorin 7A on keratinocytes induces interleukin-8 production by monocytes
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DOI：
10.1016/j.jdermsci.2011.02.004
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发表时间：
2011-06-01
影响因子：
4.6
通讯作者：
Sato, Shinichi
中科院分区：
文献类型：
--
作者：
Kamata, Masahiro;Tada, Yayoi;Sato, Shinichi
背景资料：Semaphorin 7A（Sema 7A）通过其受体α 1 β 1整合素刺激单核细胞分泌细胞因子，目的：研究Sema 7A在皮肤炎症中的作用，探讨Sema 7A在皮肤炎症中的作用。通过流式细胞术和免疫印迹研究了各种细胞因子对角质形成细胞Sema 7A表达的调节。将表达β 1-整联蛋白的人单核细胞系THP-1细胞与多聚甲醛固定的正常人表皮角质形成细胞（NHK）共培养，并研究THP-1细胞的IL-8产生。结果：IFN-γ和TNF-α轻微增加NHK上Sema 7A的表达，而IL-4降低其表达，TGF-β 1最显著增加NHK上Sema 7A的表达。当NHK被TGF-β 1刺激，多聚甲醛固定，并与THP-1细胞共培养时，与仅THP-1细胞相比，THP-1细胞的IL-8产生增加。当THP-1细胞用β 1-整联蛋白阻断抗体预处理时，THP-1细胞产生IL-8的增加被抑制。同样，当NHK预处理与Sema 7A siRNA固定前和与THP-1细胞共培养，增加IL-8的生产THP-1 cells被inhibited.Conclusion：我们的研究结果表明，Sema 7A对角质形成细胞和β 1-整合素对单核细胞有助于单核细胞激活角质形成细胞内的皮肤炎症，如银屑病或伤口。(C)2011年日本皮肤病研究学会。由Elsevier爱尔兰有限公司出版。保留所有权利。
Background: Semaphorin 7A (Sema7A) expressed on activated T cells stimulates cytokine production in monocytes through its receptor, alpha 1 beta 1 integrin.Objective: To study the significance of Sema7A expressed on keratinocytes in skin inflammation where interaction between keratinocytes and beta 1-integrin expressing inflammatory cells, such as monocytes, takes place.Methods: The regulation of Sema7A expression on keratinocytes by various cytokines was studied by flow cytometry and immunoblot. beta 1-integrin expressing human monocyte cell line, THP-1 cells, were co-cultured with paraformaldehyde-fixed normal human epidermal keratinocytes (NHK) and IL-8 production by THP-1 cells was studied. The significance of beta 1-integrin or Sema7A within this cell interaction was examined by the experiments using beta 1-integrin blocking antibody or Sema7A siRNA.Results: IFN-gamma and TNF-alpha slightly increased Sema7A expression, while IL-4 decreased it. Among cytokines tested, TGF-beta 1 most strikingly increased the Sema7A expression on NHK. When NHK was stimulated by TGF-beta 1, paraformaldehyde-fixed, and co-cultured with THP-1 cells, IL-8 production by THP-1 cells was increased compared to THP-1 cells only. When THP-1 cells were pretreated with beta 1-integrin blocking antibody, this increase in IL-8 production by THP-1 cells was inhibited. Likewise, when NHK were pretreated with Sema7A siRNA before fixation and co-cultured with THP-1 cells, increase in IL-8 production by THP-1 cells was inhibited.Conclusion: Our results suggest that Sema7A on keratinocytes and beta 1-integrin on monocytes contribute to monocyte activation by keratinocytes within skin inflammation, such as psoriasis or wound. (C) 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.