Analysis of SOCS/CSI family in skin

细胞因子信号传导抑制因子(SOCS)/细胞因子诱导SH2含（CIS）蛋白是细胞因子诱导的，是STAT信号通路的负调节因子。我们研究了角化细胞（细胞因子的主要靶细胞之一）中STATs和SOCS/CIS家族的调节机制。干扰素γ(IFNγ)作用后3小时，SOCS1 mRNA表达上调，IFNγ作用后48小时，SOCS1 mRNA表达增加8.1倍。SOCS3 mRNA也从ifn γ后1小时开始上调，并且在ifn γ后6至12小时之间，SOCS3/CIS3 mRNA增加6.7倍。IL-6暴露1 h后，SOCS3/CIS3 mRNA表达增强，而SOCS1/JAB mRNA不受IL-6的诱导，IL-4上调SOCS1/JAB和CIS1 mRNA表达，IL-4后1 h， SOCS1/JAB和CIS1 mRNA表达分别增加3.4倍和5.1倍。相比之下，磷酸化STAT3的表皮生长因子（EGF）不影响SOCS/CIS家族mRNA的表达水平。转染表达SOCS1/JAB（AxCALNLJAB）的腺病毒载体完全抑制ifn γ依赖性STAT1磷酸化和il -4依赖性STAT6磷酸化。转染AxCALNLJAB不抑制il -6依赖性STAT3的磷酸化，一些报道表明SOCS1/JAB是髓性白血病Ml细胞中STAT3信号通路的有效抑制剂。转染表达SOCS3/CIS（AxCACIS3）的腺病毒载体完全抑制il -6依赖性STAT3磷酸化，部分抑制ifn - γ依赖性STAT1磷酸化。然而，转染AxCACIS3并没有抑制il -4依赖性STAT6磷酸化。转染表达CIS1的腺病毒载体（AxCALNLCISl）对正常角质形成细胞中的STAT1、STAT3和STAT6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，SOCS调节这些细胞的细胞因子信号。

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.