Up-regulation of cyclooxygenase-2 expression by TSG-6 protein in macrophage cell line |
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Authors: | Mindrescu Catalin Le Junming Wisniewski Hans-Georg Vilcek Jan |
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Affiliation: | Department of Microbiology, New York University School of Medicine, New York, USA. mindrc01@med.nyu.edu |
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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. |
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Keywords: | TSG-6 Cyclooxygenase Prostaglandins Inflammation Macrophages Hyaluronan Inter-α-inhibitor TNF-α Fertility |
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