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)
|