We studied the effect of endogenous and exogenous prostaglandin E2 (PGE2), a metabolite of arachidonic acid through the cyclooxygenase (COX) pathway, on interleukin (IL)-1 β –induced COX-2 expression, using primary cultures of human bronchial smooth-muscle cells (HBSMC). Treatment with exogenous PGE2 resulted in enhanced expression of IL-1 β –induced COX-2 protein and messenger RNA (mRNA) as compared with the effect of the cytokine per se. Inhibition of PGE2 production with a nonselective COX inhibitor (flurbiprofen, 10 μ M) resulted in a significant reduction in IL-1 β – induced COX-2 expression, supporting a role of endogenous COX metabolites in the modulation of COX-2 expression. None of the experimental conditions used in the study affected the expression of constitutive cyclooxygenase (COX-1). Treatment with cycloheximide to inhibit translation, and with dexamethasone or actinomycin D to inhibit transcription, linked the effect of PGE2 to the transcriptional level of COX-2 mRNA rather than to a potential effect on protein and/or mRNA stabilization. PGE2 increased adenylate cyclase activity in a concentration dependent manner, and forskolin, a direct activator of adenylate cyclase, caused a marked increase in IL-1 β –dependent COX-2, suggesting the existence of a causal relationship between the two events. The same results were observed with salbutamol, a bronchodilator that acts by increasing cyclic adenosine monophosphate. The effect of PGE2 on COX-2 expression may contribute to the hypothesized antiinflammatory role of PGE2 in human airways, providing a self-amplifying loop leading to increased biosynthesis of PGE2 during an inflammatory event.
Effect of Endogenous and Exogenous Prostaglandin E2 on Interleukin-1 β –Induced Cyclooxygenase-2 Expression in Human Airway Smooth-Muscle Cells
ZANNINI , PIERO;
2000-01-01
Abstract
We studied the effect of endogenous and exogenous prostaglandin E2 (PGE2), a metabolite of arachidonic acid through the cyclooxygenase (COX) pathway, on interleukin (IL)-1 β –induced COX-2 expression, using primary cultures of human bronchial smooth-muscle cells (HBSMC). Treatment with exogenous PGE2 resulted in enhanced expression of IL-1 β –induced COX-2 protein and messenger RNA (mRNA) as compared with the effect of the cytokine per se. Inhibition of PGE2 production with a nonselective COX inhibitor (flurbiprofen, 10 μ M) resulted in a significant reduction in IL-1 β – induced COX-2 expression, supporting a role of endogenous COX metabolites in the modulation of COX-2 expression. None of the experimental conditions used in the study affected the expression of constitutive cyclooxygenase (COX-1). Treatment with cycloheximide to inhibit translation, and with dexamethasone or actinomycin D to inhibit transcription, linked the effect of PGE2 to the transcriptional level of COX-2 mRNA rather than to a potential effect on protein and/or mRNA stabilization. PGE2 increased adenylate cyclase activity in a concentration dependent manner, and forskolin, a direct activator of adenylate cyclase, caused a marked increase in IL-1 β –dependent COX-2, suggesting the existence of a causal relationship between the two events. The same results were observed with salbutamol, a bronchodilator that acts by increasing cyclic adenosine monophosphate. The effect of PGE2 on COX-2 expression may contribute to the hypothesized antiinflammatory role of PGE2 in human airways, providing a self-amplifying loop leading to increased biosynthesis of PGE2 during an inflammatory event.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
