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

Research output: Contribution to journalArticle

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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

Fingerprint

Cyclooxygenase 2
Interleukin-1
Dinoprostone
Smooth Muscle Myocytes
Prostaglandin-Endoperoxide Synthases
Adenylyl Cyclases
Messenger RNA
Flurbiprofen
Cyclooxygenase 1
Cyclooxygenase Inhibitors
Albuterol
Bronchodilator Agents
Dactinomycin
Colforsin
Cycloheximide
Cyclic AMP
Dexamethasone
Proteins
Anti-Inflammatory Agents
Cytokines

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Effect of endogenous and exogenous prostaglandin E2 on interleukin-1β-induced cyclooxygenase-2 expression in human airway smooth-muscle cells. / Bonazzi, Albino; Bolla, Manlio; Buccellati, Carola; Hernandez, Alicia; Zarini, Simona; Viganò, Teresa; Fumagalli, Francesca; Viappiani, Serena; Ravasi, Saula; Zannini, Piero; Chiesa, Giuseppe; Folco, Giancarlo; Sala, Angelo.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 162, No. 6, 2000, p. 2272-2277.

Research output: Contribution to journalArticle

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, vol. 162, no. 6, pp. 2272-2277.
Bonazzi, Albino ; Bolla, Manlio ; Buccellati, Carola ; Hernandez, Alicia ; Zarini, Simona ; Viganò, Teresa ; Fumagalli, Francesca ; Viappiani, Serena ; Ravasi, Saula ; Zannini, Piero ; Chiesa, Giuseppe ; Folco, Giancarlo ; Sala, Angelo. / Effect of endogenous and exogenous prostaglandin E2 on interleukin-1β-induced cyclooxygenase-2 expression in human airway smooth-muscle cells. In: American Journal of Respiratory and Critical Care Medicine. 2000 ; Vol. 162, No. 6. pp. 2272-2277.
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AU - Bonazzi, Albino

AU - Bolla, Manlio

AU - Buccellati, Carola

AU - Hernandez, Alicia

AU - Zarini, Simona

AU - Viganò, Teresa

AU - Fumagalli, Francesca

AU - Viappiani, Serena

AU - Ravasi, Saula

AU - Zannini, Piero

AU - Chiesa, Giuseppe

AU - Folco, Giancarlo

AU - Sala, Angelo

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