title: Interleukin-1 beta increases airway epithelial cell mitogenesis partly by stimulating endothelin-1 production.
abstract: To investigate the influence of interleukin-1 beta (IL-1 beta) on airway epithelial cell growth, we measured [3H]thymidine incorporation and cell numbers of cultured porcine tracheal epithelial cells in the presence or absence of human recombinant IL-1 beta with or without the following: goat antiporcine polyclonal antibody to platelet-derived growth factor (PDGF); IL-1 receptor antagonist; indomethacin; PD-145065, a combined endothelin-A and -B receptor antagonist; BQ-123, an antagonist selective for endothelin-A receptors; or phosphoramidon, an inhibitor, in part, of endothelin-converting enzymes, including neutral endopeptidase. We found that IL-1 beta stimulated the proliferation of airway epithelial cells, and this response was inhibited by the IL-1 receptor antagonist and by PD-145065 or BQ-123. However, neither indomethacin nor PDGF antibody was influential. The endothelin receptor antagonists also decreased basal thymidine incorporation by these cells as did phosphormidon, although to a lesser degree. Data from radioimmunoassays indicated that phosphormidon reduced the endogenous production of endothelin-1 from the cells, and IL-1 beta clearly increased it over time. We conclude that IL-1 beta is a stimulant of airway epithelial cell growth, and its mitogenic effects are mediated, in part, by endogenous endothelin-1 production.
authors.affiliation: Lung Cell Biology Laboratories, Rush University, Chicago, Illinois, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Murlas
authors.forename: A C
authors.initials: AC
authors.lastname: Sharma
authors.forename: A
authors.initials: A
authors.lastname: Gulati
authors.forename: F
authors.initials: F
authors.lastname: Najmabadi
mesh_terms: D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects; D019332:Endothelin-1 / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical; D013552:Swine; D014132:Trachea / Q000166:cytology*
chemical_list: D019332:Endothelin-1; D007375:Interleukin-1; D011994:Recombinant Proteins