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Induction of endogenous interleukin 1 alpha limits to one cycle the proliferative response to FGF
Author(s) -
Prudovsky Igor,
Poole Ashleigh,
Cooper Emily,
Kacer Doreen
Publication year - 2015
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/fasebj.29.1_supplement.726.8
Subject(s) - fibroblast growth factor , microbiology and biotechnology , cancer research , chemistry , biology , receptor , biochemistry
We found that transient FGF stimulation of various cell types results in the novel phenomenon termed “FGF memory” – a sustained blockage of efficient proliferative response to FGF, PDGF or EGF. FGF memory establishment requires HDAC activity, indicating its epigenetic character. FGF treatment stimulates the proinflammatory NFkappaB signaling, which is also critical for FGF memory formation. The search of potential FGF‐induced mediators of FGF memory revealed that FGF induces a sustained expression of the inflammatory cytokine IL1alpha, and this induction is abolished by HDAC inhibitors. Similarly to FGF pretreatment, transient cell treatment with recombinant IL1alphainhibits the proliferative response to further FGF stimulation. However, cells pretreated with FGF or IL1alpha exhibit an enhanced restructuring of actin cytoskeleton and migration in response to FGF. IL1alpha‐prestimulated cells respond to FGF treatment by ERK1/2 phosphorylation and expression of cyclin D1, but not of cyclin A. Both IRAP, a specific inhibitor of IL1 receptor, and neutralizing anti‐IL1alphaantibodies prevent the formation of FGF memory and rescue an efficient proliferative response to FGF restimulation. Thus, FGF memory is mediated by the endogenous IL1alpha. It may play a role in the limitation of proliferative response to tissue damage and prevention of wound‐induced hyperplasia.