Up-regulation of cyclooxygenase-2 expression by TSG-6 protein in macrophage cell line.
TNF-stimulated gene 6 (TSG-6) encodes a 35 kDa inducible secreted glycoprotein important in inflammation and female fertility. Previous studies have shown that TSG-6 has anti-inflammatory activity in models of acute and chronic inflammation. In the present study, we show that treatment of the RAW 264.7 murine macrophage cell line with TSG-6 protein up-regulates the expression of inducible cyclooxygenase-2 (COX-2), a key enzyme in inflammation and immune responses. This action of TSG-6 protein was abolished by heat denaturation, trypsin digestion, or anti-TSG-6 antibodies. TSG-6 treatment also resulted in a rapid increase in COX-2 mRNA levels, suggesting that TSG-6 up-regulates COX-2 gene expression. Up-regulation of COX-2 was accompanied by an increase in the production of prostaglandins, especially PGD2. As the PGD2 metabolite, 15-deoxy-Delta12,14-PGJ2, can act as a negative regulator of inflammation, these TSG-6 actions may explain, at least in part, the anti-inflammatory effect of TSG-6 observed in the intact organism.
Mindrescu
Catalin
C
Department of Microbiology, New York University School of Medicine, New York, USA. mindrc01@med.nyu.edu
Le
Junming
J
Wisniewski
Hans-Georg
HG
Vilcek
Jan
J
D000818:Animals; D015815:Cell Adhesion Molecules / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D044967:Serum; D015854:Up-Regulation / Q000187:drug effects
D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D011453:Prostaglandins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C072273:TNFAIP6 protein, human; C513057:Tnfaip6 protein, mouse; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases