Analysis of SOCS/CSI family in skin

细胞因子信号传导抑制因子（SOCS）/含丝氨酸诱导型SH 2（CIS）蛋白是丝氨酸诱导型的，并且是STAT信号传导途径的负调节因子。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，发现SOCS 1 mRNA在IFNγ作用后3 h上调，IFN γ作用后48 h上调8.1倍。SOCS 3 mRNA也从IFN γ后1 h开始上调，SOCS 3/CIS 3 mRNA在IFN γ后6 - 12 h增加6.7倍。IL-6处理1h后，SOCS 3/CIS 3 mRNA表达增强，而SOCS 1/JAB mRNA表达不受IL-6诱导; IL-4处理1h后，SOCS 1/JAB和CIS 1 mRNA表达分别增加3.4倍和5.1倍。相反，表皮生长因子（EGF）磷酸化STAT 3，不影响SOCS/CIS家族mRNA的表达水平。表达SOCS 1/JAB的腺病毒载体（AxCALNLJAB）的转染完全抑制IFNγ依赖的STAT 1磷酸化和IL-4依赖的STAT 6磷酸化。AxCANNLJAB的转染并不抑制IL-6依赖性STAT 3磷酸化--多份报告显示SOCS 1/JAB是骨髓白血病M1细胞中STAT 3信号传导的有效抑制剂。转染表达SOCS 3/CIS的腺病毒载体（AxCACIS 3）完全抑制IL-6依赖性STAT 3磷酸化，部分抑制IFNγ依赖性STAT 1磷酸化。然而，AxCACIS 3的转染不抑制IL-4依赖性STAT 6磷酸化。表达CIS 1的腺病毒载体（AxCALNLCIS 1）的转染对正常角质形成细胞中的STAT 1、STAT 3和STAT 6信号传导没有影响。因此，STAT和SOCS之间的关系在角质形成细胞中是独特的，并且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.