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Autoinhibition of IL‐15 Expression in KC Cells is ERK1/2 and PI3K Dependent
Author(s) -
Zhang S.Q.,
Luo X.,
Yang S.,
Liu J.L.,
Yang C.J.,
Yin X.Y.,
Huang H.L.,
Zhang X.J.
Publication year - 2008
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2008.02150.x
Subject(s) - signal transduction , pi3k/akt/mtor pathway , microbiology and biotechnology , cytokine , western blot , mutant , interleukin 4 , proinflammatory cytokine , biology , endogeny , interleukin , monoclonal antibody , messenger rna , chemistry , antibody , immunology , gene , biochemistry , inflammation
Interleukin (IL)‐15 is a proinflammatory cytokine and plays a key role in many diseases, including psoriasis. Although its signal transduction pathways in keratinocytes (KC) have been partially elucidated, the effects of IL‐15 on expression of IL‐15, IL‐6 and TNF‐α in KC are unknown. We have investigated the effects of IL‐15 on the expression of the three genes in primary culture of KC by the real‐time PCR, Western blot and ELISA. We observed that exogenous IL‐15 suppressed the endogenous expression of IL‐15, decreased the expression of IL‐6 at mRNA and protein levels in KC. The inhibition was blocked by anti‐IL‐15 monoclonal antibody and by inactive IL‐15, I50D mutant IL‐15. In contrast, IL‐15 increased TNF‐α transcription in these cells. Mechanistic studies demonstrated that the auto‐regulation of IL‐15 expression was dependent on activity of ERK1/2 and PI3K. Our studies suggest that there is an auto‐inhibitory mechanism controlling cellular IL‐15 levels.