title: Protective effect of nedocromil sodium on the interleukin-1-induced production of interleukin-8 in human bronchial epithelial cells.
abstract: Cellular constituents of the bronchial mucosa may participate in the recruitment of polymorphonuclear leukocytes to the inflamed airways through the generation of the neutrophil chemotactic peptide, interleukin-8 (IL-8). One important aspect of this interaction could be represented by the ability of pulmonary monokines, particularly IL-1, to induce gene expression of IL-8 in bronchial epithelial cells. In this study, we have evaluated the constitutive and IL-1-induced production of IL-8 by cultured human bronchial epithelial cells and examined the ability of the anti-inflammatory drug, nedocromil sodium, to inhibit the cytokine synthesis and release. Northern blot analysis demonstrated that IL-1 beta-treated human bronchial epithelial cells expressed appreciable levels of IL-8 mRNA during a period of 8 hours. This finding was associated with an increased release of immunoreactive IL-8 to the culture media, as assessed by specific ELISA. The bronchial epithelial cell-derived IL-8 demonstrated specific biologic activity, since the supernatants of stimulated bronchial epithelial cells possessed neutrophil chemotactic activity that could be inhibited by an antibody against human IL-8. Nedocromil sodium reduced the IL-1-induced release of IL-8 in a dose-dependent manner, but concentrations of the compounds, up to 10(-5) mol/L, did not affect the constitutive production of this cytokine.
authors.affiliation: Diagnostic Center for Respiratory and Allergic Diseases, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Vittori
authors.forename: F
authors.initials: F
authors.lastname: Sciacca
authors.forename: F
authors.initials: F
authors.lastname: Colotta
authors.forename: A
authors.initials: A
authors.lastname: Mantovani
authors.forename: S
authors.initials: S
authors.lastname: Mattoli
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015152:Blotting, Northern; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured / Q000187:drug effects / Q000276:immunology; D002633:Chemotaxis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D004347:Drug Interactions; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D017835:Nedocromil; D015363:Quinolones / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D016209:Interleukin-8; D015363:Quinolones; D011994:Recombinant Proteins; D017835:Nedocromil