Analysis of SOCS/CSI family in skin

细胞因子信号转导抑制因子(SOCS)/细胞因子诱导SH2蛋白(CIS)是细胞因子诱导的蛋白，是STAT信号通路的负调控因子。我们研究了细胞因子的主要靶细胞之一角质形成细胞中STATs和SOCS/CIS家族的调控机制。干扰素γ(干扰素γ)作用3h后，SOCS1mRNA表达上调，48h后SOCS1mRNA表达增加8.1倍。在干扰素γ后1h，SOCS3mRNA表达上调，而在干扰素γ后6~12h，SOCS3/Cis3mRNA表达增加6.7倍。白介素6(IL-6)作用1h后，SOCS3/Cis3mRNA表达增强，而SOCS1/Jab mRNA表达不受IL-6诱导，IL-4作用1h后，SOCS1/JAB和Cis1mRNA表达分别增加3.4倍和5.1倍。转染腺病毒载体(AxCALNLJAB)可完全抑制干扰素γ依赖的STAT1磷酸化和IL-4依赖的STAT6磷酸化。转染AxCALNLJAB不能抑制依赖IL-6的STAT3的磷酸化--一些报道表明SOCS1/JAB是髓系白血病ML细胞中STAT3信号的有效抑制者。转染腺病毒载体可完全抑制IL-6依赖的STAT3的磷酸化，部分抑制干扰素γ依赖的STAT1的磷酸化。然而，转导AxCACIS3并不能抑制依赖IL-4的STAT6的磷酸化。转染腺病毒载体(AxCALNLCIS1)对正常角质形成细胞中的STAT1、STAT3和STAT6信号转导无影响。因此，STAT和SOCS之间的关系在角质形成细胞中是独一无二的，SOCS调节这些细胞中的细胞因子信号。

The suppressor of cytokine signaling (SOCS)/cytokine-inducible SH2 containing (CIS) proteins are cytokine-inducible and are negative regulators of the STAT signaling pathway. We investigated the mechanism regulating STATs and the SOCS/CIS family in keratinocytes, one of the major target cells for cytokines.SOCS1 mRNA was upregulated 3 h post- interferon γ(IFNγ), and a 8.1-fold increase in SOCS1 mRNA occurred 48 h post-IFNγ. SOCS3 mRNA was also upregulated from 1 h post-IFNγ, and a 6.7-fold increase in SOCS3/CIS3 mRNA occurred between 6 and 12 h post-INFγ. Interleukin-6 (IL-6) exposure for 1 h enhanced the expression of SOCS3/CIS3 mRNA, but SOCS1/JAB mRNA was not induced by IL-6, IL-4 upregulated SOCS1/JAB and CIS1 mRNA, with 3.4-and 5.1-fold increases in mRNA observed at 1 h post-IL-4, respectively. In contrast, epidermal growth factor(EGF), which phosphorylates STAT3, did not influence the level of SOCS/CIS family mRNA expression.Transfection of an adenovirus vector expressing SOCS1/JAB(AxCALNLJAB)completely inhibited IFNγ-dependent STAT1 phosphorylation and IL-4-dependent STAT6 phosphorylation. Transfection of AxCALNLJAB did not inhibit IL-6-dependent STAT3 phosphorylation-several reports show SOCS1/JAB is a potent inhibitor of STAT3 signaling in the myeloid leukemia Ml cell. Transfection of the adenovirus vector expressing SOCS3/CIS(AxCACIS3)completely inhibited IL-6-dependent STAT3 phosphorylation and partially inhibited IFNγ-dependent STAT1 phosphorylation. However, transfection of AxCACIS3 did not inhibit IL-4-dependent STAT6 phosphorylation. Transfection of the adenovirus vector expressing CIS1(AxCALNLCISl)had no effect on STAT1, STAT3, and STAT6 signaling in normal keratinocytes. Therefore, the relationship between STAT and SOCS is unique in the keratinocytes, and SOCS regulates cytokine signals in these cells.