AJP - Lung Cellular and Molecular Physiology, Vol 273, Issue 1 193-L200, Copyright © 1997 by American Physiological Society

ARTICLES

IL-1 beta inhibits ET-1 production by ATII cells in vitro: evidence for involvement of cyclooxygenase 2 pathway

C. Odoux, B. Crestani, G. Lebrun, C. Rolland, P. Aubin, T. Fournier, J. Fiet and M. Aubier
Institut National de la Sante et de la Recherche Medicale U408, Faculte Xavier Bichat, Paris, France.

The aim of this study was to characterize the effect of alveolar macrophage (AM) secretory products on endothelin (ET)-1 production by rat alveolar type II (ATII) cells in primary culture. We quantified preproendothelin (ppET)-1 mRNA by Northern blot and ET-1 concentrations in cell supernatants by enzyme-linked immunosorbent assay. Conditioned medium (CM) from rat adherent AM decreased the ppET-1 mRNA levels in ATII cells and reduced ET-1 concentrations in cell culture supernatants. This effect was mediated by interleukin (IL)-1 beta as shown by pretreatment of CM with an anti-IL-1 beta neutralizing antiserum. IL-1 beta effect was dependent on protein synthesis, was partially prevented with indomethacin, and was totally prevented with dexamethasone. Specific inhibition of cyclooxygenase 2 activity completely reversed the effect of IL-1 beta. We conclude that rat AM inhibit ET-1 production by rat ATII cells in vitro through IL-1 beta secretion. The IL-1 beta-mediated inhibition is dependent on the cyclooxygenase 2 pathway. Downregulation of ET-1 production by activated AM could limit the intra-alveolar burden of this profibrogenic peptide and thus could prevent fibrosis development.

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