The S100A8/A9 heterodimer amplifies proinflammatory cytokine production by macrophages via activation of nuclear factor kappa B and p38 mitogen-activated protein kinase in rheumatoid arthritis.

Arthritis Research & Therapy
Katsue SunahoriH Makino

Abstract

S100A8 and S100A9, two Ca2+-binding proteins of the S100 family, are secreted as a heterodimeric complex (S100A8/A9) from neutrophils and monocytes/macrophages. Serum and synovial fluid levels of S100A8, S100A9, and S100A8/A9 were all higher in patients with rheumatoid arthritis (RA) than in patients with osteoarthritis (OA), with the S100A8/A9 heterodimer being prevalent. By two-color immunofluorescence labeling, S100A8/A9 antigens were found to be expressed mainly by infiltrating CD68+ macrophages in RA synovial tissue (ST). Isolated ST cells from patients with RA spontaneously released larger amounts of S100A8/A9 protein than did the cells from patients with OA. S100A8/A9 complexes, as well as S100A9 homodimers, stimulated the production of proinflammatory cytokines, such as tumor necrosis factor alpha, by purified monocytes and in vitro-differentiated macrophages. S100A8/A9-mediated cytokine production was suppressed significantly by p38 mitogen-activated protein kinase (MAPK) inhibitors and almost completely by nuclear factor kappa B (NF-kappaB) inhibitors. NF-kappaB activation was induced in S100A8/A9-stimulated monocytes, but this activity was not inhibited by p38 MAPK inhibitors. These results indicate that the S100A8/A...Continue Reading

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Citations

Feb 7, 2008·Proceedings of the National Academy of Sciences of the United States of America·Fredrik JohanssonKarin E Bornfeldt
Sep 13, 2008·Journal of Virology·Thomas E MorrisonMark T Heise
Jan 10, 2013·Investigative Ophthalmology & Visual Science·Qiuchan DengXi Huang
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Methods Mentioned

BETA
enzyme-linked immunosorbent assay
ELISA
density gradient centrifugation
FCS
protein assay

Software Mentioned

NIH Image
ImageJ
CBA

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