IL-1 beta inhibits ET-1 production by ATII cells in vitro: evidence for involvement of cyclooxygenase 2 pathway.
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.
Odoux
C
C
Institut National de la Santé et de la Recherche Médicale U408, Faculté Xavier Bichat, Paris, France.
Crestani
B
B
Lebrun
G
G
Rolland
C
C
Aubin
P
P
Fournier
T
T
Fiet
J
J
Aubier
M
M
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D051546:Cyclooxygenase 2; D003609:Dactinomycin / Q000494:pharmacology; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D016232:Endothelins / Q000096:biosynthesis*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011498:Protein Precursors / Q000096:biosynthesis*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017077:Culture Media, Conditioned; D019332:Endothelin-1; D016232:Endothelins; D007375:Interleukin-1; D015850:Interleukin-6; D007527:Isoenzymes; D008565:Membrane Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases