Down-regulation of inducible nitric oxide synthase by lysophosphatidic acid in human respiratory epithelial cells
Down-regulation of inducible nitric oxide synthase by lysophosphatidic acid in human respiratory epithelial cells
复制标题
DOI：
10.1023/b:mcbi.0000038215.89821.7f
复制
发表时间：
2004-07-01
影响因子：
4.3
通讯作者：
Shimizu, E
中科院分区：
文献类型：
--
作者：
Kadowaki, S;Chikumi, H;Shimizu, E
病毒感染通常导致呼吸道上皮细胞中的诱导型一氧化氮合酶（iNOS或NOS 2）被炎性细胞因子激活。活化的NOS 2催化一氧化氮（NO）的合成，其过量可导致细胞损伤。另一方面，溶血磷脂酸（LPA），一种从损伤组织中的上皮细胞、血小板和成纤维细胞释放的脂质介质，在细胞损伤的修复中起作用。然而，LPA修复机制的细节仍然未知。我们证明了LPA有利于修复的一个效果，特别是抑制由人呼吸道上皮细胞在体外的尼古丁诱导的NOS 2蛋白和mRNA的表达。LPA处理的，姜黄素刺激的细胞的NO产生也减少。这些降低通过用Y-27632抑制Rho激酶来防止。因此，通过LPA下调精氨酸诱导的NOS 2活性增加可能涉及Rho依赖性信号传导途径。NO在病毒性呼吸道感染中的有害生物学效应可能通过涉及LPA或Rho的治疗操作来改变。
Viral infection generally results in the activation of inducible nitric oxide synthase (iNOS or NOS2) in respiratory epithelial cells by inflammatory cytokines. Activated NOS2 catalyzes synthesis of nitric oxide (NO), which in excess can cause cellular injury. On the other hand, lysophosphatidic acid (LPA), a lipid mediator released from epithelial cells, platelets, and fibroblasts in injured tissue, functions in repair of cell injury. However, details of the mechanism for repair by LPA remain unknown. We demonstrated one effect of LPA favoring repair, specifically inhibition by LPA of cytokine-induced NOS2 protein and mRNA expression by human respiratory epithelial cells in vitro. NO production by LPA-treated, cytokine-stimulated cells was also reduced. These decreases were prevented by Rho kinase inhibition with Y-27632. Thus, down-regulation by LPA of cytokine-induced increases in NOS2 activity is likely to involve a Rho-dependent signaling pathway. Harmful biologic effects of NO in viral respiratory infection might be modified by therapeutic manipulations involving LPA or Rho.