title: Divergent effects of nitric oxide on airway epithelial cell activation.
abstract: Nitric oxide (NO*) is a gaseous mediator synthesized by nitric oxide synthases. NO* is involved in the modulation of inflammation, but its role in airway inflammation remains controversial. We investigated the role of NO* in the synthesis of the chemokines interleukin-8 and monocyte chemotactic protein-1, and of intercellular adhesion molecule-1 by human airway epithelial cells. normal human bronchial epithelial cells and the bronchial epithelial cell line BEAS-2B were used. interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) secretion and intercellular adhesion molecule-1 (ICAM-1) expression were measured by ELISA. mRNA was assessed by semiquantitative RTI-PCR. Interleukin-8 secretion was significantly reduced after 24h incubation with the NO* donor, sodium nitroprusside. The effect was dose-dependent. Similar results were obtained with S-nitroso-N-D,L-penicillamine and S-nitroso-L-glutathione. Inhibition of endogenous NO* with the nitric oxide synthase inhibitor N-nitro-L-arginine-methyl-ester caused an increase in IL-8 secretion by lipopolysaccharide- and cytokine-stimulated BEAS-2B cells. Sodium nitroprusside also caused a reduction in monocyte chemotactic protein-1 secretion by both cell types. In contrast, intercellular adhesion molecule-1 expression was upregulated by sodium nitroprusside. RTI-PCR results indicate that the modulation of protein levels was paralleled by modification in mRNA levels. NO* has divergent effects on the synthesis of different inflammatory mediators in human bronchial epithelial cells.
authors.affiliation: Laboratorio di Biología Cellulare Respiratoria, Dipartimento Cardiotoracico e Vascolare, University of Pisa, Via Paradisa 2, Pisa, Italy. t.neri@med.unipi.it
authors.forename: Tommaso
authors.initials: T
authors.lastname: Neri
authors.forename: Ilaria
authors.initials: I
authors.lastname: Conti
authors.forename: Chiara
authors.initials: C
authors.lastname: Cerri
authors.forename: Laura
authors.initials: L
authors.lastname: Tavanti
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Paggiaro
authors.forename: Alessandro
authors.initials: A
authors.lastname: Celi
mesh_terms: D001980:Bronchi / Q000166:cytology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000032:analysis / Q000096:biosynthesis*; D058501:Enzyme-Linked Immunospot Assay; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000032:analysis / Q000096:biosynthesis*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D018932:Chemokine CCL2; D018836:Inflammation Mediators; D016209:Interleukin-8; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide