TSG-6 protein binding to glycosaminoglycans: formation of stable complexes with hyaluronan and binding to chondroitin sulfates.
TSG-6 protein, up-regulated in inflammatory lesions and in the ovary during ovulation, shows anti-inflammatory activity and plays an essential role in female fertility. Studies in murine models of acute inflammation and experimental arthritis demonstrated that TSG-6 has a strong anti-inflammatory and chondroprotective effect. TSG-6 protein is composed of the N-terminal link module that binds hyaluronan and a C-terminal CUB domain, present in a variety of proteins. Interactions between the isolated link module and hyaluronan have been studied extensively, but little is known about the binding of full-length TSG-6 protein to hyaluronan and other glycosaminoglycans. We show that TSG-6 protein and hyaluronan, in a temperature-dependent fashion, form a stable complex that is resistant to dissociating agents. The formation of such stable complexes may underlie the activities of TSG-6 protein in inflammation and fertility, e.g. the TSG-6-dependent cross-linking of hyaluronan in the cumulus cell-oocyte complex during ovulation. Because adhesion to hyaluronan is involved in cell trafficking in inflammatory processes, we also studied the effect of TSG-6 on cell adhesion. TSG-6 binding to immobilized hyaluronan did not interfere with subsequent adhesion of lymphoid cells. In addition to immobilized hyaluronan, full-length TSG-6 also binds free hyaluronan and all chondroitin sulfate isoforms under physiological conditions. These interactions may contribute to the localization of TSG-6 in cartilage and to its chondroprotective and anti-inflammatory effects in models of arthritis.
Wisniewski
Hans-Georg
HG
Department of Microbiology, New York University School of Medicine, New York, New York 10016, USA. hans-georg.wisniewski@med.nyu.edu <hans-georg.wisniewski@med.nyu.edu>
Snitkin
Evan S
ES
Mindrescu
Catalin
C
Sweet
Moshe H
MH
Vilcek
Jan
J
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D019921:Biotinylation; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002645:Chickens; D002809:Chondroitin Sulfates / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000737:chemistry; D005260:Female; D006025:Glycosaminoglycans / Q000737:chemistry*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007249:Inflammation; D007313:Insecta; D007477:Ions; D007700:Kinetics; D051379:Mice; D009865:Oocytes / Q000378:metabolism; D010053:Ovary / Q000378:metabolism; D010060:Ovulation; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D013696:Temperature; D013997:Time Factors; D015854:Up-Regulation
D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D006025:Glycosaminoglycans; D007477:Ions; D020033:Protein Isoforms; C072273:TNFAIP6 protein, human; C513057:Tnfaip6 protein, mouse; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates; D004492:Edetic Acid