title: Hypersecretion of mucin in response to inflammatory mediators by guinea pig tracheal epithelial cells in vitro is blocked by inhibition of nitric oxide synthase.
abstract: Primary cultures of guinea pig tracheal epithelial cells in air/liquid interface were exposed to one of four agents associated with airway inflammation: the peptide histamine (100 microM), the lipid mediator platelet-activating factor (1 microM), the cytokine tumor necrosis factor-alpha (15 ng/ml; specific activity 2.86 x 10(7) U/mg), or enzymatically generated reactive oxygen species (purine [500 microM]+xanthine oxidase [20 mU/ml]). Effects of each of these substances on release of mucin by guinea pig tracheal epithelial (GPTE) cells were measured using a monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA). Each secretagogue significantly enhanced release of mucin, but the stimulatory effect of each was inhibited by pre-(+)co-incubation of the cells with the competitive inhibitor of nitric oxide synthase, NG-monomethyl-L-arginine (L-NMA), but not by NG-monomethyl-D-arginine (D-NMA), the inactive stereoisomer that does not inhibit nitric oxide synthase. Neither L-NMA nor D-NMA affected mucin secretion by themselves. The results suggest that each of these inflammation-associated mediators provokes airway epithelial mucin secretion via a mechanism involving intracellular production of nitric oxide (NO) as a critical signaling molecule.
authors.affiliation: Department of Anatomy, Physiological Sciences and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh 27606, USA.
authors.forename: K B
authors.initials: KB
authors.lastname: Adler
authors.forename: B M
authors.initials: BM
authors.lastname: Fischer
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: N H
authors.initials: NH
authors.lastname: Choe
authors.forename: D T
authors.initials: DT
authors.lastname: Wright
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D018836:Inflammation Mediators / Q000494:pharmacology*; D009077:Mucins / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010972:Platelet Activating Factor / Q000187:drug effects; D012636:Secretory Rate / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D014132:Trachea / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D019323:omega-N-Methylarginine
chemical_list: D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D009077:Mucins; D010972:Platelet Activating Factor; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D019323:omega-N-Methylarginine; D006632:Histamine; D001120:Arginine; D019001:Nitric Oxide Synthase