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Crosslinking
of CD44 on Rheumatoid Synovial Cells Augment Interleukin 6 Production |
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Koichi Fujii,
Yoshiya Tanaka, Stefan Hübscher, Kazuyoshi Saito, Toshiyuki Ota, and
Sumiya Eto |
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First
Department of Internal Medicine (KF, YT, KS, SE), University of Occupational
and Environmental Health, Japan School of Medicine, Kitakyushu, Japan; Department
of Pathology (SH), University of Birmingham, Birmingham, United Kingdom;
and the Department of Clinical Laboratory (TO), University of Occupational
and Environmental Health, Japan School of Medicine, Kitakyushu, Japan |
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SUMMARY: CD44 is a ubiquitous
molecule also known as hyaluronic acid or homing receptor. However, its
cellular functions and its role in inflammation, for example rheumatoid
synovitis, are currently unknown. Here we propose a novel function for CD44.
Using synovial cells from patients with rheumatoid arthritis (RA), we demonstrated
that CD44 crosslinking and binding to hyaluronan augmented IL-6 production.
Briefly, we found that (a) rheumatoid synovial cells highly expressed CD44;
(b) crosslinking of CD44 augmented IL-6 production and its mRNA transcription;
(c) hyaluronan, especially when fragmented, also increased IL-6 production;
and (d) CD44 activated the transcription factor activator protein-1 and
CAMP-responsive element binding protein. These results indicate that the
adhesion of RA synovial cells to matrices such as hyaluronic acid through
CD44 could activate transcription factor, resulting in cytokine production.
We therefore propose that the function of adhesion molecules as a signaling
molecule may be pivotal in the pathogenesis of inflammation, including RA
synovitis.
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