CD40 MEDIATED ACTIVATION OF GINGIVAL AND PERIODONTAL-LIGAMENT FIBROBLASTS

CD40 Is A 50 KDA TRANSMEMBRANE PROTEIN important for regulating B lymp hocyte proliferation and differentiation. This novel activation antige n is primarily expressed by hematopoietic cells including B lymphocyte s, follicular dendritic cells, and monocytes. Recently, human fibrobla sts from a variety of tissues were shown to display CD40; however, its function was unknown. Cellular responses mediated by CD40 are natural ly triggered by its counter-receptor, the CD40 ligand, which is displa yed on activated T cells, mast cells, eosinophils, basophils, and B li neage cells. This study investigated the functional significance of CD 40 expression on periodontal fibroblasts, in the context of periodonta l inflammation. The experiments reported herein demonstrate constituti ve CD40 expression on cultured periodontal Ligament (PDL) and gingival fibroblasts. Interestingly, cells of gingival origin displayed up to 13-fold higher constitutive levels of CD40, versus fibroblasts from PD L. Interferon gamma (IFN gamma) treatment enhanced CD40 expression on PDL and gingival fibroblasts, with up to 61-fold induction of expressi on. Immunohistochemical staining was used to detect CD40 on fibroblast ic cells in both normal and acutely inflamed gingival tissue. Expressi on of CD40 in inflamed tissue was significantly higher than in uninfla med tissue. Western blot analysis of anti-CD40 triggered cells reveale d the induction of tyrosine phosphorylation on a 50 kDa protein in PDL and gingival fibroblasts. These results indicate that CD40 is an acti ve signaling conduit in periodontal fibroblasts. This concept was furt her substantiated by the fact that CD40 engagement stimulated interleu kin 6 (IL-6) production by gingival fibroblasts, but not periodontal l igament fibroblasts. Overall, these results demonstrate that CD40 on p eriodontal fibroblasts may functionally interact with CD40L-expressing cells. This CD40/CD40L interaction can stimulate fibroblast activatio n and synthesis of the proinflammatory cytokine IL-6.