Combined Effect of Cigarette Smoke and Mineral Fibers on the Gene Expression of Cytokine mRNA Yasuo Morimoto,1 Tohru Tsuda,1 Hajime Hori,2 Hiroshi Yamato,3 Akira Ohgami,3 Toshiaki Higashi,4 Nobuhiko Nagata,5 Masamitsu Kido,5 and Isamu Tanaka3 1Department of Occupational Pneumology, Institute of Industrial Ecological Sciences
2School of Health Sciences; 3Department of Environmental Health Engineering, Institute of Industrial Ecological Sciences; 4Department of Work Systems and Health, Institute of Industrial Ecological Sciences; and 5Department of Respiratory Diseases, University of Occupational and Environmental Health, Japan, Kitayushu, Japan 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-1 (IL-1) , interleukin-6 (IL-6) , and tumor necrosis factor- (TNF) 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-1 mRNA levels in AMs. Chrysotile stimulated the expression of IL-1, TNF, and IL-6 in AMs, and the expression of bFGF in lungs. RF1 resulted in increased expression of IL-1 and TNF in AMs. Cigarette smoke stimulated the gene expression of iNOS in AMs and IL-6 and bFGF in lungs treated with chrysotile ; IL-1 in AMs and bFGF in lungs did the same in lungs with RF1. Among these cytokines, message levels of IL-1, 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-1, iNOS, and bFGF would be the possible parameters of the lung remodeling induced by mineral fibers. Key words: alveolar macrophage, bFGF, ceramic fiber, chrysotile, IL-1, IL-6, iNOS, lung, Mn-SOD, TNF. Environ Health Perspect 107:495-500 (1999) . [Online 7 May 1999] http://ehpnet1.niehs.nih.gov/docs/1999/107p495-500morimoto/ abstract.html Address correspondence to Y. Morimoto, Department of Occupational Pneumology, Institute of Industrial and Ecological Sciences, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Yahatanishi, Kitakyushu, Japan. Telephone: +81 93 691 7466. Fax: +81 93 691 4284. E-mail: yasuom@med.uoeh-u.ac.jp We thank M. Tsunoda and M. Hirohashi for assistance with some of the experiments. This work was supported in part by the Ministry of Education and Science in Japan, the Fukuoka Cancer Society, and the Uehara Memorial Foundation. Received 17 December 1997 ; accepted 8 February 1999. The full version of this article is available for free in HTML format. |