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Suppressor of cytokine signaling 1 inhibits IFN‐γ inflammatory signaling in human keratinocytes by sustaining ERK1/2 activation
Author(s) -
Madonna Stefania,
Scarponi Claudia,
De Pità Ornella,
Albanesi Cristina
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-106831
Subject(s) - suppressor of cytokine signaling 1 , suppressor of cytokine signalling , socs3 , signal transduction , stat protein , cytokine , microbiology and biotechnology , stat1 , janus kinase 1 , interferon gamma , mapk/erk pathway , proinflammatory cytokine , kinase , stat3 , phosphorylation , chemistry , biology , janus kinase , immunology , inflammation , suppressor , biochemistry , gene
ABSTRACT IFN‐γ is a pleiotropic cytokine importantly involved in the development of skin inflammatory responses. Epidermal keratinocytes are extremely susceptible to IFN‐γ action, but, once transduced with the suppressors of cytokine signaling (SOCS)1 molecule, they can no longer express a number of IFN‐γ‐inducible signal transducer and activator of transcription (STAT)1‐dependent genes. Extracellular‐signal‐regulated kinase (ERK)1/2 pathway is also involved in the protection of keratinocytes from the proinflammatory effect of IFN‐γ. Here we show that, after IFN‐γ stimulation, SOCS1 inhibited IFN‐γ receptor and STAT1 phosphorylation but maintained ERK1/2 activation. SOCS1 was also necessary for the IFN‐γ‐induced RAS and Raf‐1 activities in keratinocytes. The enhanced ERK1/2 pathway in SOCS1‐overexpressing keratinocytes was in part responsible for their inability to respond to IFN‐γ, in terms of CXCL10 and CCL2 production, and for the high production of CXCL8. Moreover, SOCS1 interacted with the RAS inhibitor p120 RasGAP and promoted its degradation after IFN‐γ stimulation. We hypothesize that SOCS1 functions as suppressor of IFN‐γ signaling, not only by inhibiting STAT1 activation but also by sustaining ERK1/2‐dependent antiinflammatory pathways.—Madonna, S., Scarponi, C., De Pità, O., Albanesi, C. Suppressor of cytokine signaling 1 inhibits IFN‐γ inflammatory signaling in human keratinocytes by sustaining ERK1/2 activation. FASEB J. 22, 3287–3297 (2008)