Crosslinking of CD44 on rheumatoid synovial cells augment interleukin 6 production

CD44 is a ubiquitous molecule also known as hyaluronic acid or homing recep tor. However, its cellular functions and its role in inflammation, for exam ple rheumatoid synovitis, are currently unknown. Here we propose a novel fu nction for CD44. Using synovial cells from patients with rheumatoid arthrit is (RA), we demonstrated that CD44 crosslinking and binding to hyaluronan a ugmented IL-6 production. Briefly, we found that (a) rheumatoid synovial ce lls highly expressed CD44; (b) crosslinking of CD44 augmented IL-6 producti on and its mRNA transcription; (c) hyaluronan, especially when fragmented, also increased IL-6 production; and (d) CD44 activated the transcription fa ctor activator protein-1 and CAMP-responsive element binding protein. These results indicate that the adhesion of RA synovial cells to matrices such a s hyaluronic acid through CD44 could activate transcription factor, resulti ng in cytokine production. We therefore propose that the function of adhesi on molecules as a signaling molecule may be pivotal in the pathogenesis of inflammation, including RA synovitis.