Fibroblast growth factor-1 (FGF-1) enhances IL-2 production and nuclear translocation of NF-kappa B in FGF receptor-bearing Jurkat T cells

Fibroblast growth factors (PGFs) are heparin-binding proteins crucial to em bryogenesis, angiogenesis, and wound healing, FGF-1 is abundantly expressed in the synovium in rheumatoid arthritis and in rejecting allografts, sites of chronic immune-mediated inflammation, The frequency of FGF-1-responsive T cells is increased in the peripheral blood of these disorders, and a hig h percentage of infiltrating T cells in rheumatoid arthritis synovium expre ss receptors for FGF-1, To understand the action of FGF-1 in T cells, studi es were initiated in Jurkat T cells that express the signaling isoform of F GF receptor-1, These experiments show that FGF-1 stimulation of Jurkat T ce lls provides a second signal that augments TCR-mediated IL-2 production. An alogous to costimulation via CD28, this activity is mediated through activa tion of Rel/kappa B, a family of transcription factors known to regulate IL -2 and other activation-inducible proteins. FGF-1 alone induces modest nucl ear translocation of kappa B-binding proteins, and this translocation is en hanced by the combination of anti-CD3 and FGF-1. This NF-kappa B binding co mplex is composed of transcriptionally active p65(RelA)/p50 heterodimers an d results primarily from the targeted degradation of I kappa B-alpha, an in hibitor that sequesters Rel/kappa B in the cytoplasm, These data are the fi rst to show a connection between FGF-1 signaling and NF-kappa B activation outside of embryonic development. The signaling events that link FGF recept or-1 engagement and NF-kappa B activation in Jurkat are probably distinct f rom the CD28 costimulation pathway, since FGF-1-induced Rel/kappa B binding proteins do not contain significant levels of c-Rel and are not identical with the CD28 response complex.