title: Direct exposure to nitrogen dioxide fails to induce the expression of some inflammatory cytokines in an IC-21 murine macrophage cell model.
abstract: Biologically-active molecules secreted from alveolar macrophages, such as cytokines, have been proposed to be involved in the induction of pulmonary toxicity and inflammation in response to the inhalation of oxidant gas pollutants such as NO2 and O3. Despite this, mechanistic studies are hampered by the difficulty in obtaining control macrophages from human subjects, and the intrinsic variability of such primary cells. It is, thus, of importance to develop alternative models for such studies. Here, we have characterised expression kinetics of the mRNAs for tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), macrophage inflammatory protein-1 alpha (MIP-1 alpha) and macrophage inflammatory protein-1 beta (MIP-1 beta) in confluent cultures of the murine IC-21 macrophage line in response to LPS. The secretion of TNF-alpha protein into the medium, assayed by L-929 cell bioassay, closely followed the expression of its mRNA in response to the LPS stimulus. In contrast to LPS, the exposure of IC-21 cells to either air or various concentrations of NO2 in air between 2 and 20 ppm, in an inverted plate exposure model, failed to induce the expression of any of the cytokine mRNAs probed. We conclude that the IC-21 cell line may represent a suitable model for studying the role of stimulated cytokine gene expression in inflammation and that the early events in the pulmonary inflammatory response to the inhalation of NO2 do not involve stimulated release of TNF-alpha, IL-1 beta or MIP-1 alpha/MIP-1 beta from macrophages.
authors.affiliation: Division of Toxicology, Karolinska Institute, Stockholm, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Tu
authors.forename: A
authors.initials: A
authors.lastname: Wallin
authors.forename: P
authors.initials: P
authors.lastname: Moldéus
authors.forename: I A
authors.initials: IA
authors.lastname: Cotgreave
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002478:Cells, Cultured; D054407:Chemokine CCL4; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006131:Growth Inhibitors / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D019402:Macrophage Inflammatory Proteins; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D015846:Monokines / Q000235:genetics / Q000378:metabolism; D009585:Nitrogen Dioxide / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D054407:Chemokine CCL4; D016207:Cytokines; D018076:DNA, Complementary; D006131:Growth Inhibitors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D009585:Nitrogen Dioxide