LIGATION OF CD40 ON FIBROBLASTS INDUCES CD54 (ICAM-1) AND CD106 (VCAM-1) UP-REGULATION AND IL-6 PRODUCTION AND PROLIFERATION

CD40 was originally described as a functionally significant B cell sur face molecule, However, CD40 is also expressed on monocytes, dendritic cells, epithelial cells, and basophils, We now report that synovial m embrane (SM) or dermal fibroblasts also express cell surface CD40 in v itro, Fibroblast CD40 expression declines with increasing time in cult ure and recombinant interferon-gamma (rINF-gamma) induces fibroblast C D40 up-regulation, This effect of rINF-gamma is augmented by recombina nt interleukin-1 alpha or recombinant tumor necrosis factor-alpha. CD4 0 expression on fibroblasts is functionally significant because CD40L- CD40 interactions induce SM fibroblast CD54 (intercellular adhesion mo lecule-1) and CD106 (vascular cell adhesion molecule-1) up-regulation, Moreover, ligation of CD40 augments IL-6 production by SM fibroblasts and induces fibroblasts to proliferate, In addition, rINF-gamma enhan ces the effect of CD40L-CD40 interactions on fibroblast proliferation, Taken together, these studies show that fibroblasts can express CD40, cytokines can regulate fibroblast CD40 expression, and CD40 ligation induces fibroblast activation and proliferation.