LUNG CYTOKINE PRODUCTION IN BLEOMYCIN-INDUCED PULMONARY FIBROSIS
LUNG CYTOKINE PRODUCTION IN BLEOMYCIN-INDUCED PULMONARY FIBROSIS
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DOI：
10.3109/01902149209020649
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发表时间：
1992-01-01
影响因子：
1.7
通讯作者：
KUNKEL, SL
中科院分区：
文献类型：
--
作者：
PHAN, SH;KUNKEL, SL
在博莱霉素诱导的肺纤维化中，肺损伤伴随炎症和随后的纤维化。 在这项研究中，在博莱霉素治疗的小鼠中测量了几种细胞因子的肺mRNA，以评估它们在肺纤维化中的作用。 在博来霉素治疗的应答CBA小鼠的肺中发现肿瘤坏死因子-α（TNF-α）和转化生长因子-β（TGF-β）mRNA的显著增加，但在无应答BALB/c小鼠中没有发现。 在博来霉素给药后第7天，应答动物的增加达到峰值，随后恢复至对照水平。 该时间过程与β-肌动蛋白mRNA增加的时间过程相同，但先于胶原I和III mRNA的峰值增加。 当分析肺巨噬细胞的细胞因子分泌时，观察到肺泡巨噬细胞和间质细胞之间以及博来霉素应答CBA和无应答BALB/c小鼠的细胞之间存在差异。 只有CBA小鼠的肺泡巨噬细胞分泌的IL-1的量增加。 CBA小鼠肺泡和间质细胞条件培养基中TNF-α活性增加，而无应答BALB/c小鼠仅肺泡巨噬细胞分泌任何活性。 对于这些不同的细胞来说，TNF-α分泌增加的动力学是不同的。 这些结果与TNF-α和TGF-β的产生增加是纤维化过程的重要组成部分的结论一致。
In bleomycin-induced pulmonary fibrosis, lung injury is accompanied with inflammation and subsequent fibrosis. In this study, lung mRNA for several cytokines was measured in bleomycin-treated mice to evaluate their roles in lung fibrosis. Significant increases in tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) mRNA were found in lungs of bleomycin-treated responder CBA mice but not in nonresponder BALB/c mice. Increases in responder animals peaked on day 7 after bleomycin administration, and subsequently returned toward control levels. This time course paralleled that for the increase in beta-actin mRNA, but preceded the peak increase in mRNA for collagens I and III. When lung macrophages were analyzed for cytokine secretion, differences were observed between alveolar macrophages and interstitial cells, and between cells from bleomycin-responsive CBA and nonresponsive BALB/c mice. Only alveolar macrophages from CBA mice secreted increased amounts of IL-1. TNF-alpha activity was increased in conditioned media of alveolar and interstitial cells of CBA mice, while only alveolar macrophages of nonresponder BALB/c mice secreted any activity. The kinetics of the increased secretion of TNF-alpha was dissimilar for these different cells. These results are consistent with the conclusion that increased production of TNF-alpha and TGF-beta is an important component of the fibrotic process.