Morimoto Y, Tsuda T, Hori H, Yamato H, Ohgami A, Higashi T, Nagata N, Kido M, Tanaka I
Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan, Yahatanishi, Kitakyushu, Japan.
Environ Health Perspect. 1999 Jun;107(6):495-500. doi: 10.1289/ehp.99107495.
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[alpha] (IL-1[alpha]), interleukin-6 (IL-6), and tumor necrosis factor-[alpha] (TNF[alpha]) 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[alpha] mRNA levels in AMs. Chrysotile stimulated the expression of IL-1[alpha], TNF[alpha], and IL-6 in AMs, and the expression of bFGF in lungs. RF1 resulted in increased expression of IL-1[alpha] and TNF[alpha] in AMs. Cigarette smoke stimulated the gene expression of iNOS in AMs and IL-6 and bFGF in lungs treated with chrysotile; IL-1[alpha] in AMs and bFGF in lungs did the same in lungs with RF1. Among these cytokines, message levels of IL-1[alpha], 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[alpha], iNOS, and bFGF would be the possible parameters of the lung remodeling induced by mineral fibers.
为了研究矿物纤维刺激哪些参数以及香烟烟雾是否增强纤维诱导的反应，我们在体内检测了暴露于矿物纤维和香烟烟雾的大鼠肺泡巨噬细胞（AM）和肺组织中细胞因子mRNA的水平。雄性Wistar大鼠经气管内单次注入2mg国际癌症研究机构（IARC）温石棉或难熔陶瓷纤维（RF1）。然后，动物每周5天吸入侧流烟雾，持续4周。使用半定量逆转录聚合酶链反应评估来自暴露于矿物纤维和/或香烟烟雾的大鼠的脂多糖刺激的AM和肺组织中锰超氧化物歧化酶、诱导型一氧化氮合酶（iNOS）、碱性成纤维细胞生长因子（bFGF）、白细胞介素-1α（IL-1α）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNFα）mRNA的表达。仅暴露于香烟烟雾会增加AM中IL-1αmRNA水平。温石棉刺激AM中IL-1α、TNFα和IL-6的表达以及肺组织中bFGF的表达。RF1导致AM中IL-1α和TNFα表达增加。香烟烟雾刺激温石棉处理的肺组织中AM中iNOS以及IL-6和bFGF的基因表达；香烟烟雾对RF1处理的肺组织中AM中IL-1α和肺组织中bFGF也有相同作用。在这些细胞因子中，IL-1α、iNOS和bFGF的信使水平在受矿物纤维刺激的大鼠中增加，并且香烟烟雾增强了矿物纤维的刺激作用。因此，IL-1α、iNOS和bFGF可能是矿物纤维诱导肺重塑的参数。
