The oxygen radical scavenger pyrrolidine dithiocarbamate enhances interleukin-1beta-induced cyclooxygenase-2 expression in cerebral microvascular smooth muscle cells.
Oxidative stress and inducible cyclooxygenase-2 (COX-2)-mediated prostaglandin (PG) formation have been proposed to play an important role in cytokine-induced vascular pathology. To explore the relationship between oxidative stress and COX-2 induction, cultured murine cerebral microvascular smooth muscle cells (SMCs) were stimulated with interleukin-1beta (IL-1beta) in the presence or absence of an oxygen radical scavenger, pyrrolidine dithiocarbamate (PDTC). IL-1beta increased COX-2 protein expression in a dose- and time-dependent manner, an increase that was further enhanced by PDTC in a dose-dependent manner. PDTC did not, however, affect the expression of COX-1 protein. In the presence of 100 microM PDTC, PGE(2) production induced by IL-1beta (5 ng/ml) was increased by threefold as compared with IL-1beta alone. Although PDTC enhanced COX-2 protein expression, it did not increase IL-1beta-induced expression of COX-2 mRNA, indicating that the regulatory effect occurred at the posttranscriptional level. The time course of COX-2 protein degradation indicated that PDTC also did not alter the stability of the COX-2 protein induced by IL-1beta. These results suggest that endogenous oxygen radicals may blunt COX-2 induced by IL-1beta through an effect on translation.
Fang
Xiang
X
Department of Biochemistry, University of Iowa College of Medicine, Iowa City, IA 52242, USA. xiang-fang@uiowa.edu
Chen
Ping
P
Moore
Steven A
SA
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005609:Free Radicals; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D009130:Muscle, Smooth / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D012260:Ribonucleases / Q000378:metabolism; D013687:Telencephalon / Q000378:metabolism; D013859:Thiocarbamates / Q000494:pharmacology*; D013997:Time Factors
D000975:Antioxidants; D016166:Free Radical Scavengers; D005609:Free Radicals; D007375:Interleukin-1; D007527:Isoenzymes; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D012260:Ribonucleases; D010100:Oxygen