FSTL1 promotes arthritis in mice by enhancing inflammatory cytokine/chemokine expression.
FSTL1 promotes arthritis in mice by enhancing inflammatory cytokine/chemokine expression.
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DOI：
10.1002/art.33422
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发表时间：
2012-04
影响因子：
--
通讯作者：
Hirsch, Raphael
中科院分区：
文献类型：
--
作者：
Chaly, Yury;Marinov, Anthony D.;Oxburgh, Leif;Bushnell, Daniel S.;Hirsch, Raphael
Follistatin-like protein 1 (FSTL-1) is a secreted glycoprotein that exacerbates murine arthritis and is overexpressed in human arthritis. The aim of this study was to determine the mechanism by which FSTL-1 promotes arthritis. Collagen-induced arthritis (CIA) was induced in mice hypomorphic for FSTL-1, created with a gene trap-targeted mutant embryonic stem cell line. Arthritis was assessed by measuring paw swelling and using a qualitative arthritic index. Bone marrow-derived mesenchymal stromal cells (MSC) from hypomorphic mice, as well as mouse stromal ST2 cells transduced with short hairpin RNA to suppress FSTL-1 expression, were stimulated with interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α) and IL-17. The monocyte cell line U937, which does not express FSTL-1, was transfected with a plasmid encoding FSTL-1 and stimulated with PMA and LPS. Cell supernatants were assayed for IL-6, IL-8, monocyte chemotactic protein-1 (MCP-1), and FSTL-1 by ELISA. FSTL-1 hypomorphic mice had reduced FSTL-1 compared to littermate controls. Following induction of arthritis, a significant correlation was observed between serum FSTL-1 levels and both paw swelling and the arthritic index. A similar correlation was observed between the amount of FSTL-1 produced by MSC, stromal ST2 cells, and monocytes and the secretion of IL-6, IL-8, and MCP-1. These findings demonstrate that FSTL-1 upregulates proinflammatory mediators important in the pathology of arthritis and that serum levels of FSTL-1 correlate with severity of arthritis. The latter supports the possibility that FSTL-1 might be a target for treatment of certain forms of arthritis.
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