Tumor necrosis factor-inducible gene 6 protein also known as TNF-stimulated gene 6 protein or TSG-6 is a protein[5] that in humans is encoded by the TNFAIP6 (tumor necrosis factor, alpha-induced protein 6) gene.[6][7]
Structure and function
TSG-6 is a 30 kDa secreted protein that contains a hyaluronan-binding LINK domain a and thus is a member of the hyaluronan-binding protein family, also called hyaladherins. The hyaluronan-binding domain is known to be involved in extracellular matrix stability and cell migration. This protein has been shown to form a stable, covalent complex with inter-alpha-inhibitor (IαI), and thus enhance the serine protease inhibitory activity of IαI, which is important in the protease network associated with inflammation. The expression of this gene can be induced by a number of signalling molecules, principally tumor necrosis factor α (TNF-α) and interleukin-1 (IL-1). The expression can also be induced by mechanical stimuli in vascular smooth muscle cells, and is found to be correlated with proteoglycan synthesis and aggregation.[7] TSG-6 has been shown to modulate macrophage plasticity and signal the transition of LPS-treated macrophages from pro- to anti-inflammatory phenotype.[8]
Milner CM, Higman VA, Day AJ (June 2006). "TSG-6: a pluripotent inflammatory mediator?". Biochemical Society Transactions. 34 (Pt 3): 446–50. doi:10.1042/BST0340446. PMID16709183.
Wisniewski HG, Burgess WH, Oppenheim JD, Vilcek J (June 1994). "TSG-6, an arthritis-associated hyaluronan binding protein, forms a stable complex with the serum protein inter-alpha-inhibitor". Biochemistry. 33 (23): 7423–9. doi:10.1021/bi00189a049. PMID7516184.
Wisniewski HG, Hua JC, Poppers DM, Naime D, Vilcek J, Cronstein BN (February 1996). "TNF/IL-1-inducible protein TSG-6 potentiates plasmin inhibition by inter-alpha-inhibitor and exerts a strong anti-inflammatory effect in vivo". Journal of Immunology. 156 (4): 1609–15. PMID8568267.
Kohda D, Morton CJ, Parkar AA, Hatanaka H, Inagaki FM, Campbell ID, Day AJ (September 1996). "Solution structure of the link module: a hyaluronan-binding domain involved in extracellular matrix stability and cell migration". Cell. 86 (5): 767–75. doi:10.1016/S0092-8674(00)80151-8. PMID8797823.
Parkar AA, Kahmann JD, Howat SL, Bayliss MT, Day AJ (May 1998). "TSG-6 interacts with hyaluronan and aggrecan in a pH-dependent manner via a common functional element: implications for its regulation in inflamed cartilage". FEBS Letters. 428 (3): 171–6. doi:10.1016/S0014-5793(98)00523-7. PMID9654129.
Mindrescu C, Le J, Wisniewski HG, Vilcek J (May 2005). "Up-regulation of cyclooxygenase-2 expression by TSG-6 protein in macrophage cell line". Biochemical and Biophysical Research Communications. 330 (3): 737–45. doi:10.1016/j.bbrc.2005.03.040. PMID15809059.
