Role of tumour necrosis factor stimulated gene 6 (TSG-6) in the coupling of inter-alpha-trypsin inhibitor to hyaluronan in human follicular fluid

Abstract

Binding of the plasma proteinase inhibitor inter-␣-trypsin inhibitor (ITI) to hyaluronan is necessary for normal expansion of the cumulus-oocyte complex. Lack of ITI causes severe infertility. Binding of ITI to hyaluronan depends on calcium ions and coupling activity present in follicular fluid (Ødum et al., 2002). The complexes formed by this process contain ITI heavy chains bound to hyaluronan, and bikunin is detached from ITI during the coupling reaction. In the present study, an electrophoretic technique by which hyaluronan-bound ITI is immobilized was used to demonstrate that tumour necrosis factor stimulated gene 6 (TSG-6) is necessary for the coupling reaction. Thus, immunoprecipitation of TSG-6 in human follicular fluid eliminates the coupling reaction and re-addition restores the activity. However, it appears that components other than hyaluronan, ITI, calcium ions and TSG-6 are involved in the coupling reaction, as in vitro incubation of these components does not generate stable complexes between ITI heavy chains and hyaluronan unless some follicular fluid is added. In conclusion, TSG-6 is necessary for the coupling of ITI to hyaluronan, but at least one additional component in follicular fluid is essential.

TSG-6: a multifunctional protein associated with inflammation

“…A recent paper reports that immunoprecipitation of TSG-6 from follicular fluid inhibits the covalent coupling of IαI heavy chains to HA, but that other components of the follicular fluid are also necessary for this transfer reaction (Jessen and Ødum, 2003). More importantly, characterization of female TSG-6-knockout mice has revealed that they do not form the cumulus matrix that is required for successful ovulation/fertilization of oocytes and that they are completely sterile (Fülöp et al, 2003).…”

Structural Analysis of Bikunin Glycosaminoglycan

“…15,22,24,26 During the past decade, the interest in structural analysis of bikunin GAG has increasingly shifted from purely academic to diagnostic and therapeutic. 15,16,[28][29][30][31][32][33] The bikunin GAG structure has been demonstrated to vary, depending on the physiological or pathophysiological conditions. A disaccharide composition analysis of the urinary bikunin GAGs obtained from a septic shock patient showed a significantly lower ratio of sulfated to unsulfated disaccharides: 1:6.2 as opposed to 1:1.8 in normal plasma.…”

The extracellular matrix protein ITIH5 is a novel prognostic marker in invasive node-negative breast cancer and its aberrant expression is caused by promoter hypermethylation

“…ITI molecules consist of three protein chains: one ITI light chain, also referred to as bikunin, and two ITI heavy chains (ITIHs) (Enghild et al, 1991). The transfer of ITIHs onto HA requires tumour necrosis factor a-induced protein 6 (TNFAIP6), also known as TNF-stimulated gene 6 (Jessen and Odum, 2003). TNFAIP6 forms a stable complex (Rugg et al, 2005) with ITIH and HA during the transesterification reaction (Sanggaard et al, 2005).…”