Acidic fibroblast growth factor in synovial cells

Objective. To characterize the production and regulation of acidic fibrobla st growth factor (aFGF) in type B (fibroblast-like) synoviocytes cultured f rom both inflammatory and noninflammatory synovial lesions. Methods, Immunohistochemistry, Western blotting, and reverse transcriptase- polymerase chain reaction were used to examine the expression of aFGF by sy novial cells in vitro, Incorporation of H-3-thymidine by NIH3T3 cells in th e presence or absence of neutralizing antibody to aFGF was used to measure bioactive aFGF levels in culture media, Results. Acidic FGF was detected in all synovial cell lines during growth i n vitro; however, synoviocytes from rheumatoid arthritis (RA) patients sust ained more abundant production of cytoplasmic and nuclear aFGF, Acidic FGF production persisted after multiple passages and did not depend on the pres ence of serum, Both RA and noninflammatory synovial cells were competent to release aFGF into the media, even though aFGF lacks a signal peptide. Tumo r necrosis factor alpha, interleukin-6, and epidermal growth factor did not increase aFGF expression in vitro; in contrast, transforming growth factor beta 1 (TGF beta 1) was found to markedly increase aFGF production by cult ured synovial cells. Conclusion. Acidic FGF synthesis and release is a component of synovial cel l growth that is markedly increased in RA, TGF beta 1, and not proinflammat ory cytokines, is a potent inducer of aFGF production by synoviocytes in vi tro. These findings suggest that in RA, interactions between TGF beta 1 and aFGF may contribute to angiogenesis and fibroblast proliferation, potentia lly independently of inflammatory mediators.