Cross-linking of CD44 on rheumatoid synovial cells up-regulates VCAM-1

CD44 is a ubiquitous molecule also known as hyaluronic acid or homing recep tor. However, the cellular functions and its role in inflammation, for exam ple, rheumatoid synovitis, are currently unknown, In this study, we propose a novel function for CD44, Using synovial cells from rheumatoid arthritis (RA) patients, we demonstrated that CD44 cross-linking and binding to hyalu ronan augmented VCAM-1 expression and subsequently VCAM-1-mediated cell adh esion. Briefly, we found that 1) rheumatoid synovial cells highly expressed CD44; 2) cross-linking of CD44 markedly but transiently augmented VCAM-1 e xpression and its mRNA transcription much more than did IL-1 beta and TNF-a lpha; 3) hyaluronan, especially when fragmented, also up-regulated VCAM-1; 4) CD44 activated the transcription factor AP-1; and 5) the integrin-depend ent adhesive function of RA synovial cells to T cells was also amplified by CD44 cross-linking. These results indicate that the adhesion of RA synovia l cells to matrices such as hyaluronic acid through CD44 could up-regulate VCAM-1 expression and VCAM-1-mediated adhesion to T cells, which might in t urn cause activation of T cells and synovial cells in RA synovitis, We ther efore propose that such cross-talking among distinct adhesion molecules may be involved in the pathogenesis of inflammation, including RA synovitis.