Effect of endogenous and exogenous prostaglandin E2 on interleukin-1β-induced cyclooxygenase-2 expression in human airway smooth-muscle cells

Albino Bonazzi, Manlio Bolla, Carola Buccellati, Alicia Hernandez, Simona Zarini, Teresa Viganò, Francesca Fumagalli, Serena Viappiani, Saula Ravasi, Piero Zannini, Giuseppe Chiesa, Giancarlo Folco, Angelo Sala

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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)-1β-induced COX-2 expression, using primary cultures of human bronchial smooth-muscle cells (HBSMC). Treatment with exogenous PGE2 resulted in enhanced expression of IL-1β-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 μM) resulted in a significant reduction in IL-1β-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-1β-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.

Original languageEnglish
Pages (from-to)2272-2277
Number of pages6
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume162
Issue number6
Publication statusPublished - 2000

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ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Bonazzi, A., Bolla, M., Buccellati, C., Hernandez, A., Zarini, S., Viganò, T., Fumagalli, F., Viappiani, S., Ravasi, S., Zannini, P., Chiesa, G., Folco, G., & Sala, A. (2000). Effect of endogenous and exogenous prostaglandin E2 on interleukin-1β-induced cyclooxygenase-2 expression in human airway smooth-muscle cells. American Journal of Respiratory and Critical Care Medicine, 162(6), 2272-2277.