LPS-induced proinflammatory cytokine expression in human airway epithelial cells and macrophages via NF-B, STAT3 or AP-1 activation
LPS-induced proinflammatory cytokine expression in human airway epithelial cells and macrophages via NF-B, STAT3 or AP-1 activation
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DOI：
10.3892/mmr.2018.8542
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发表时间：
2018-04-01
影响因子：
3.4
通讯作者：
Zhao, Peng
中科院分区：
文献类型：
--
作者：
Liu, Xuefang;Yin, Sugai;Zhao, Peng
脂多糖（LPS）是革兰氏阴性菌的主要外表面膜成分，是慢性阻塞性肺疾病等几种肺部疾病发病的主要病因之一。呼吸上皮和巨噬细胞通过细胞因子的分泌，构成了外部环境和宿主对细菌感染反应之间的动态界面。本研究探讨了LPS诱导人肺细胞和巨噬细胞炎症反应的机制。研究了LPS暴露对人肺黏液表皮样癌H292细胞和人巨噬细胞THP-1细胞中细胞因子产生、炎症相关转录因子和细胞内信号通路激活的影响。结果表明，LPS显著提高了H292细胞中白细胞介素(IL)-6、IL-8、肿瘤坏死因子(TNF)-、基质金属肽酶(MMP)-9和组织金属蛋白酶抑制剂-1的表达，同时增加了分化的THP-1细胞中IL-6、IL-8和TNF-的产生。此外，LPS暴露激活了H292细胞中的核因子(NF)-B和激活蛋白(AP)-1信号，同时激活了THP-1细胞中的NF-B和信号换能器和转录激活因子（STAT） 3信号。此外，用NF-B、AP-1或STAT3抑制剂治疗可显著降低脂多糖介导的细胞中IL-8和TNF-的表达，表明这些途径可能在脂多糖诱导的细胞因子表达中起关键作用。综上所述，LPS刺激H292和THP-1细胞诱导细胞因子表达和NF-B、丝裂原活化蛋白激酶和Janus激酶/STAT3通路激活，随后NF-B、AP-1和STAT3的核易位，这表明NF-B、AP-1和STAT3在治疗与慢性炎症相关的病症和疾病中具有潜力。
Lipopolysaccharide (LPS), the major outer surface membrane component of Gram-negative bacteria, is one of the main etiological factors in the pathogenesis of several lung diseases, such as chronic obstructive pulmonary disease. The respiratory epithelium and the macrophages comprise the dynamic interface between the outside environment and the host response to bacterial infection via cytokine secretion. In the present study, the mechanisms of LPS induced-inflammatory response in human lung cells and macrophages were investigated. The effects of LPS exposure on cytokine production, inflammation-related transcription factors and intracellular signaling pathway activation were assessed in human lung mucoepidermoid carcinoma H292 cells and human macrophage THP-1 cells. The results demonstrated that LPS markedly increased the expression of interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-, matrix metallopeptidase (MMP)-9 and tissue inhibitor of metalloproteinases-1 in H292 cells, while it increased the production of IL-6, IL-8 and TNF- in differentiated THP-1 cells. In addition, LPS exposure activated nuclear factor (NF)-B and activator protein (AP)-1 signaling in H292 cells, while it activated NF-B and signal transducer and activator of transcription (STAT) 3 signaling in THP-1 cells. Furthermore, treatment with NF-B, AP-1 or STAT3 inhibitors significantly decreased the LPS-mediated expression of IL-8 and TNF- in these cells, suggesting that these pathways might serve crucial roles in LPS-induced cytokine expression. In conclusion, LPS stimulation of H292 and THP-1 cells induced cytokine expression and NF-B, mitogen-activated protein kinase and Janus kinase/STAT3 pathway activation with subsequent nuclear translocation of NF-B, AP-1 and STAT3, which demonstrated potential of the use of NF-B, AP-1 and STAT3 in therapies for conditions and diseases associated with chronic inflammation.