Abstract
TSG-6 expression is upregulated in many cell types in response to a variety of proinflammatory mediators and growth factors. This protein is detected in several inflammatory disease states (e.g. rheumatoid arthritis) and in the context of inflammation-like processes, such as ovulation, and is often associated with extracellular matrix remodelling. TSG-6 has anti-inflammatory and chondroprotective effects in various models of inflammation and arthritis, which suggest that it is a component of a negative feedback loop capable of downregulating the inflammatory response. Growing evidence also indicates that TSG-6 acts as a crucial factor in ovulation by influencing the expansion of the hyaluronan-rich cumulus extracellular matrix in the preovulatory follicle. TSG-6 is a member of the Link module superfamily and binds to hyaluronan (a vital component of extracellular matrix), as well as other glycosaminoglycans, via its Link module. In addition, TSG-6 forms both covalent and non-covalent complexes with inter-alpha-inhibitor (a serine protease inhibitor present at high levels in serum) and potentiates its anti-plasmin activity.
Highlights
Tumor necrosis factor (TNF)-stimulated gene 6 (TSG-6), which maps to human chromosome 2q23.3 (Lee et al, 1993a; Nentwich et al, 2002), was originally identified as a cDNA derived from TNF-treated human fibroblasts (Lee et al, 1990; Lee et al, 1992)
The synthesis of TSG-6 mRNA and protein is tightly regulated in a wide variety of cell types
It is becoming clear that TSG-6 is produced in inflammation-like processes, such as ovulation (Fülöp et al, 1997) and cervical ripening (Fujimoto et al, 2002), where its expression is probably induced by prostaglandin E2 (PGE2) (Fujimoto et al, 2002; Ocshner et al, 2003)
Summary
TSG-6 expression is upregulated in many cell types in response to a variety of proinflammatory mediators and growth factors. This protein is detected in several inflammatory disease states (e.g. rheumatoid arthritis) and in the context of inflammation-like processes, such as ovulation, and is often associated with extracellular matrix remodelling. TSG-6 has anti-inflammatory and chondroprotective effects in various models of inflammation and arthritis, which suggest that it is a component of a negative feedback loop capable of downregulating the inflammatory response. TSG-6 is a member of the Link module superfamily and binds to hyaluronan (a vital component of extracellular matrix), as well as other glycosaminoglycans, via its Link module.
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