Mattoli S, Colotta F, Fincato G, Mezzetti M, Mantovani A, Patalano F, Fasoli A
Laboratorio di Biologia Cellulare e Molecolare Polmonare, Università di Milano, Italia.
J Cell Physiol. 1991 Nov;149(2):260-8. doi: 10.1002/jcp.1041490212.
We have previously demonstrated that human bronchial epithelial cells release appreciable amounts of interleukin 1 (IL1) and interleukin 6 (IL6) when exposed to toluene diisocyanate (TDI) in vitro. TDI is an inflammatory and asthmogenic stimulus presumed to act at least in part through immunological mechanisms. The epithelial cell-derived IL1 and IL6 can promote T cell activation and proliferation in culture, and if this also happens in vivo they may contribute to the persistence of the inflammatory response of the bronchial mucosa observed in TDI-sensitive asthmatics. In this study, we confirmed the release of biologically active IL1 beta and IL6-like substances from bronchial epithelial cells exposed to isocyanates in vitro, and related the rate and the magnitude of the cytokine secretion with the pattern of IL1 beta and IL6 gene expression and the extent of epithelial cell injury. In the epithelial cell cultures exposed to TDI, there was a parallel, progressive increase in the expression of IL6 mRNA and in the secretion of IL6 protein between 48 hours and 6 days after exposure. By contrast, although increasing amounts of biologically active IL1 beta were detected in the supernatants of TDI-exposed epithelial cells throughout the 6-day period following exposure, augmented levels of IL1 beta mRNA were only evident 6 days after exposure, suggesting that TDI exposure might have initially affected the enzymatic cleavage of the intracellular IL1 beta precursor and the mechanisms which regulate the secretion of mature IL1 beta.
我们之前已经证明，人支气管上皮细胞在体外暴露于甲苯二异氰酸酯（TDI）时会释放相当数量的白细胞介素1（IL1）和白细胞介素6（IL6）。TDI是一种炎症和致哮喘刺激物，推测至少部分通过免疫机制起作用。上皮细胞衍生的IL1和IL6可促进培养中的T细胞活化和增殖，如果这在体内也发生，它们可能有助于在TDI敏感哮喘患者中观察到的支气管黏膜炎症反应的持续存在。在本研究中，我们证实了体外暴露于异氰酸酯的支气管上皮细胞释放具有生物活性的IL1β和IL6样物质，并将细胞因子分泌的速率和幅度与IL1β和IL6基因表达模式以及上皮细胞损伤程度相关联。在暴露于TDI的上皮细胞培养物中，暴露后48小时至6天之间，IL6 mRNA表达和IL6蛋白分泌呈平行、渐进性增加。相比之下，虽然在暴露后6天的整个期间，在暴露于TDI的上皮细胞上清液中检测到越来越多具有生物活性的IL1β，但IL1β mRNA水平仅在暴露后6天明显升高，这表明TDI暴露可能最初影响了细胞内IL1β前体的酶促切割以及调节成熟IL1β分泌的机制。
