Up-regulation of cyclooxygenase-2 expression by TSG-6 protein in macrophage cell line.

Abstract

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.

• Authors: Catalin Mindrescu, Junming Le, Hans-Georg Wisniewski, Jan Vilcek
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 330 Issue 3 Pg. 737-45 (May 13 2005) ISSN: 0006-291X [Print] United States
• PMID: 15809059 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Adhesion Molecules
• Membrane Proteins
• Prostaglandins
• RNA, Messenger
• Recombinant Proteins
• TNFAIP6 protein, human
• Tnfaip6 protein, mouse
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases

Topics

• Animals
• Cell Adhesion Molecules (pharmacology)
• Cell Line
• Cyclooxygenase 2
• Gene Expression Regulation, Enzymologic (drug effects)
• Humans
• Macrophages (drug effects, enzymology, metabolism)
• Membrane Proteins
• Mice
• Prostaglandin-Endoperoxide Synthases (genetics, metabolism)
• Prostaglandins (metabolism)
• RNA, Messenger (genetics, metabolism)
• Recombinant Proteins (pharmacology)
• Serum
• Up-Regulation (drug effects)