Yenepoya Research Centre, Yenepoya University, Deralakatte, Mangalore, Karnataka, 575018, India.
Inflammation. 2019 Aug;42(4):1160-1169. doi: 10.1007/s10753-019-01010-4.
Acute lung injury (ALI) is characterized by acute inflammation and tissue injury results in dysfunction of the alveolar epithelial membrane. If the epithelial injury is severe, a fibroproliferative phase of ALI can develop. During this phase, the activated fibroblast and myofibroblasts synthesize excessive collagenous extracellular matrix that leads to a condition called pulmonary fibrosis. Lung injury can be caused by several ways; however, the present review focus on bleomycin (BLM)-mediated changes in the pathology of lungs. BLM is a chemotherapeutic agent and has toxic effects on lungs, which leads to oxidative damage and elaboration of inflammatory cytokines. In response to the injury, the inflammatory cytokines will be activated to defend the system from injury. These cytokines along with growth factors stimulate the proliferation of myofibroblasts and secretion of pathologic extracellular matrix. During BLM injury, the pro-inflammatory cytokine such as IL-17A will be up-regulated and mediates the inflammation in the alveolar epithelial cell and also brings about recruitment of certain inflammatory cells in the alveolar surface. These cytokines probably help in up-regulating the expression of p53 and fibrinolytic system molecules during the alveolar epithelial cells apoptosis. Here, our key concern is to provide the adequate knowledge about IL-17A-mediated p53 fibrinolytic system and their pathogenic progression to pulmonary fibrosis. The present review focuses mainly on IL-17A-mediated p53-fibrinolytic aspects and how curcumin is involved in the regulation of pathogenic progression of ALI and pulmonary fibrosis.
急性肺损伤（ALI）的特征是急性炎症和组织损伤导致肺泡上皮膜功能障碍。如果上皮损伤严重，可能会发展为 ALI 的纤维增生期。在这个阶段，激活的成纤维细胞和成肌纤维细胞合成过多的胶原细胞外基质，导致肺纤维化。肺损伤可能由多种途径引起；然而，本综述重点关注博莱霉素（BLM）介导的肺部病理学变化。BLM 是一种化疗药物，对肺部有毒性作用，导致氧化损伤和炎症细胞因子的产生。为了应对损伤，炎症细胞因子将被激活，以保护系统免受损伤。这些细胞因子与生长因子一起刺激成肌纤维细胞的增殖和病理性细胞外基质的分泌。在 BLM 损伤中，促炎细胞因子如 IL-17A 将被上调，并介导肺泡上皮细胞的炎症，也会引起肺泡表面某些炎症细胞的募集。这些细胞因子可能有助于在肺泡上皮细胞凋亡过程中上调 p53 和纤维蛋白溶解系统分子的表达。在这里，我们主要关注的是提供关于 IL-17A 介导的 p53 纤维蛋白溶解系统及其在肺纤维化发病机制中的知识。本综述主要集中在 IL-17A 介导的 p53-纤维蛋白溶解方面，以及姜黄素如何参与 ALI 和肺纤维化发病机制的调节。
