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 (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-1β (IL-1β) in the presence or absence of an oxygen radical scavenger, pyrrolidine dithiocarbamate (PDTC). IL-1β 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 μM PDTC, PGE₂ production induced by IL-1β (5 ng/ml) was increased by threefold as compared with IL-1β alone. Although PDTC enhanced COX-2 protein expression, it did not increase IL-1β-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-1β. These results suggest that endogenous oxygen radicals may blunt COX-2 induced by IL-1β through an effect on translation.