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

Byrd VM, Ballard DW, Miller GG, Thomas JW
J Immunol. 1999 162 (10): 5853-9

PMID: 10229820

Fibroblast growth factors (FGFs) are heparin-binding proteins crucial to embryogenesis, 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 high percentage of infiltrating T cells in rheumatoid arthritis synovium express receptors for FGF-1. To understand the action of FGF-1 in T cells, studies were initiated in Jurkat T cells that express the signaling isoform of FGF receptor-1. These experiments show that FGF-1 stimulation of Jurkat T cells provides a second signal that augments TCR-mediated IL-2 production. Analogous to costimulation via CD28, this activity is mediated through activation of Rel/kappaB, a family of transcription factors known to regulate IL-2 and other activation-inducible proteins. FGF-1 alone induces modest nuclear translocation of kappaB-binding proteins, and this translocation is enhanced by the combination of anti-CD3 and FGF-1. This NF-kappaB binding complex is composed of transcriptionally active p65(RelA)/p50 heterodimers and results primarily from the targeted degradation of IkappaB-alpha, an inhibitor that sequesters Rel/kappaB in the cytoplasm. These data are the first to show a connection between FGF-1 signaling and NF-kappaB activation outside of embryonic development. The signaling events that link FGF receptor-1 engagement and NF-kappaB activation in Jurkat are probably distinct from the CD28 costimulation pathway, since FGF-1-induced Rel/kappaB binding proteins do not contain significant levels of c-Rel and are not identical with the CD28 response complex.

MeSH Terms (21)

Biological Transport CD28 Antigens Cell Nucleus DNA-Binding Proteins Drug Interactions Fibroblast Growth Factor 1 Fibroblast Growth Factor 2 Humans I-kappa B Proteins Jurkat Cells NF-kappa B NF-KappaB Inhibitor alpha Proto-Oncogene Proteins Proto-Oncogene Proteins c-rel Receptor, Fibroblast Growth Factor, Type 1 Receptor Protein-Tyrosine Kinases Receptors, Fibroblast Growth Factor Response Elements Signal Transduction T-Lymphocytes Transcription, Genetic

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