Particle-Induced Cytokine Responses in Cardiac Cell Cultures—the Effect of Particles versus Soluble Mediators Released by Particle-Exposed Lung Cells

• Published in: Toxicological sciences 2008-11, Vol.106 (1), p.233-241
• Main Authors: Totlandsdal, Annike I., Refsnes, Magne, Skomedal, Tor, Osnes, Jan-Bjørn, Schwarze, Per E., Låg, Marit
• Format: Article
• Language: English
• Subjects: Animals; cardiac cells; Coculture Techniques; cocultures; Culture Media, Conditioned - metabolism; cytokines; Cytokines - metabolism; Dose-Response Relationship, Drug; Epithelial Cells - drug effects; Epithelial Cells - immunology; Fibroblasts - drug effects; Fibroblasts - immunology; Inflammation Mediators - metabolism; Interleukin-1beta - metabolism; Interleukin-6 - metabolism; Lung - drug effects; Lung - immunology; lung cells; Male; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - immunology; Paracrine Communication; Particulate Matter - toxicity; Rats; Rats, Inbred WKY; Soot - toxicity; Tumor Necrosis Factor-alpha - metabolism; ultrafine particles
• ISSN: 1096-6080; 1096-0929
• DOI: 10.1093/toxsci/kfn162

Increased levels of particulate matter have been associated with adverse effects in the respiratory as well as the cardiovascular system. The biological mechanisms behind these associations are still unresolved. Among potential mechanisms, particulate matter–associated cardiac effects may be initiated by inhaled small-sized particles, particle components and/or mediators related to inflammation that translocate into the pulmonary circulation. In the present study cytokine responses (interleukin [IL]-6, IL-1β, and tumor necrosis factor [TNF]-α) of primary rat cardiomyocytes and cardiofibroblasts in mono- and cocultures induced by direct exposure to particles, were compared with cytokine responses induced by mediators released by particle-exposed primary rat epithelial lung cells (conditioned media). Cells were exposed to a model ultrafine particle (ultrafine carbon black, Printex 90) and in selected experiments to an urban air particle sample (SRM 1648, St Louis, MO). In lung cell cultures both particle types induced release of IL-6 and IL-1β, whereas TNF-α was only detected upon exposure to St Louis particles. The release of IL-6 by cardiac cells was strongly enhanced upon exposure to conditioned media, and markedly exceeded the response to direct particle exposure. IL-1, but not TNF-α, seemed necessary, but not sufficient, for this enhanced IL-6 release. The role of IL-1 was demonstrated by use of an IL-1 receptor antagonist that partially reduced the effect of the conditioned media, and by a stimulating effect on the cardiac cell release of IL-6 by exogenous addition of IL-1α and IL-1β. These in vitro findings lend support to the hypothesis that particle-induced cardiac inflammation and disease may involve lung-derived mediators.