Combined effect of cigarette smoke and mineral fibers on the gene expression of cytokine mRNA

Abstract

To investigate which parameters are stimulated by mineral fibers and whether cigarette smoke enhanced a fiber-induced response, we examined the level of cytokine mRNA from alveolar macrophages (AMs) and lungs of rats exposed to mineral fibers and cigarette smoke in vivo. Male Wistar rats were given a single intratracheal instillation of 2 mg of Union Internationale Contre le Cancer chrysotile or refractory ceramic fiber (RF1). The animals then inhaled a side stream of smoke 5 days per week for 4 weeks. The expression of manganese superoxide dismutase, inducible nitric oxide synthase (iNOS), basic fibroblast growth factor (bFGF), interleukin-1α (IL-1α), interleukin-6 (IL-6), and tumor necrosis factor-α (TNFα) mRNA from lipopolysaccharide-stimulated AMs and lungs of rats exposed to mineral fibers and/or cigarette smoke were assessed using semiquantitative reverse-transcriptase polymerase chain reaction. Exposure only to cigarette smoke increased in IL-1α mRNA levels in AMs. Chrysotile stimulated the expression of IL-1α, TNFα, and IL-6 in AMs, and the expression of bFGF in lungs. RF1 resulted in increased expression of IL-1α and TNFα in AMs. Cigarette smoke stimulated the gene expression of iNOS in AMs and IL-6 and bFGF in lungs treated with chrysotile; IL-1α in AMs and bFGF in lungs did the same in lungs with RF1. Among these cytokines, message levels of IL-1α, iNOS, and bFGF were increased in rats stimulated with mineral fibers, and the stimulating effects of mineral fibers were enhanced by cigarette smoke. Therefore, IL-1α, iNOS, and bFGF would be the possible parameters of the lung remodeling induced by mineral fibers.