Interleukin-1 regulates keratinocyte expression of T cell targeting chemokines through interleukin-1 receptor associated kinase-1 (IRAK1) dependent and independent pathways.
Interleukin-1 regulates keratinocyte expression of T cell targeting chemokines through interleukin-1 receptor associated kinase-1 (IRAK1) dependent and independent pathways.
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DOI：
10.1016/j.cellsig.2009.01.005
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发表时间：
2009-05
影响因子：
4.8
通讯作者：
Jensen LE
中科院分区：
文献类型：
--
作者：
Sanmiguel JC;Olaru F;Li J;Mohr E;Jensen LE
IL-1 is a potent pro-inflammatory cytokine that activates intracellular signaling cascades some of which may involve IL-1 receptor associated kinase-1 (IRAK1). Psoriasis is a T cell dependent chronic inflammatory condition of the skin of unknown cause. IL-1 has been implicated in psoriasis pathology, but the mechanism has not been elucidated. Interestingly, expression of IRAK1 is elevated in psoriatic skin. To identify a potential link between IL-1, keratinocytes and T cells in skin inflammation we employed pathway-focused microarrays to evaluate IL-1 dependent gene expression in keratinocytes. Several candidate mRNAs encoding known T cell chemoattractants were identified in primary keratinocytes and the stable keratinocyte cell line HaCaT. CCL5 and CCL20 mRNA and protein levels were confirmed up-regulated by IL-1 in concentration and time-dependent manners. Furthermore IL-1 synergized with IFN-γ and TNF-α. Expression of CXCL9, CXCL10 and CXCL11 mRNAs was also increased in response to IL-1, but protein could only be detected in medium from cells treated with IFN-γ alone or in combination with IL-1. Over-expression of IRAK1 led to increased constitutive and cytokine induced production of CCL5 and CCL20. Inhibition of IRAK1 activity through RNAi or expression of a dominant negative mutant blocked production of CCL5 and CCL20 but had no effect upon the IL-1 enhancement of IFN-γ induced CXCL9, CXCL10 and CXCL11 production. In conclusion IL-1 regulates T cell targeting chemokine production in keratinocytes through IRAK1 dependent and independent pathways. These pathways may contribute to acute and chronic skin inflammation.
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影响因子：
3.5
作者：
Bowcock, AM;Shannon, W;Menter, A
通讯作者：
Menter, A
影响因子：
10.3
作者：
Lew, W;Lee, E;Krueger, JG
通讯作者：
Krueger, JG
影响因子：
5.5
作者：
O'Neill, LAJ;Greene, C
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Greene, C
影响因子：
4.4
作者：
Gottlieb, AB;Chamian, F;Krueger, JG
通讯作者：
Krueger, JG
DOI：
10.1073/pnas.071054198
发表时间：
2001-04-10
影响因子：
11.1
作者：
Li, XX;Commane, M;Stark, GR
通讯作者：
Stark, GR