| Co-Investigator(Kenkyū-buntansha) |
YAMASAKI Kenshi Ehime University, Faculty of Medicine, Instructor, 医学部, 助手 (40294798)
SHIRAKATA Yuji Ehime University, Faculty of Medicine, Instructor, 医学部, 助手 (50226320)
SAYAMA Koji Ehime University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (80187286)
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| Research Abstract |
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.
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