The oxygen radical scavenger pyrrolidine dithiocarbamate enhances interleukin-1β-induced cyclooxygenase-2 expression in cerebral microvascular smooth muscle cells

Oxidative stress and inducible cyclooxygenase-2 (COX2)-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 muM 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. (C) 2002 Elsevier Science (USA).