Suppressor of cytokine signaling 1 inhibits IFN-gamma inflammatory signaling in human keratinocytes by sustaining ERK1/2 activation.

IFN-gamma is a pleiotropic cytokine importantly involved in the development of skin inflammatory responses. Epidermal keratinocytes are extremely susceptible to IFN-gamma action, but, once transduced with the suppressors of cytokine signaling (SOCS)1 molecule, they can no longer express a number of IFN-gamma-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-gamma. Here we show that, after IFN-gamma stimulation, SOCS1 inhibited IFN-gamma receptor and STAT1 phosphorylation but maintained ERK1/2 activation. SOCS1 was also necessary for the IFN-gamma-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-gamma, 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-gamma stimulation. We hypothesize that SOCS1 functions as suppressor of IFN-gamma signaling, not only by inhibiting STAT1 activation but also by sustaining ERK1/2-dependent antiinflammatory pathways.
Mesh Terms:
Cells, Cultured, Chemokine CCL2, Chemokine CXCL10, Enzyme Activation, Humans, Interferon-gamma, Interleukin-8, Keratinocytes, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, STAT1 Transcription Factor, Signal Transduction, Suppressor of Cytokine Signaling Proteins, Up-Regulation, p120 GTPase Activating Protein, ras Proteins
FASEB J.
Date: Sep. 01, 2008
Download Curated Data For This Publication
143680
Switch View:
  • Interactions 3
  • PTM Genes 1