Lin Jinle, Tian Jun, Wang Li, Wu Weigang, Li Huaying, Wang Xueyan, Zeng Xiaobin, Zhang Wenwu
Department of Emergency and Critical Care Medicine, Baoan Hospital, Nanfang Medical University, China.
J Toxicol Sci. 2017;42(1):53-61. doi: 10.2131/jts.42.53.
Lipopolysaccharide (LPS), a Gram-negative bacterial outer membrane component, is one of the major causes of septic shock. Herein we investigate LPS-induced apoptosis of rat alveolar epithelial type II cells (AEC II) and the effects of LPS on surfactant protein-C (SP-C) expression in AEC II, along with the possible molecular mechanisms. LPS exposure impaired cell viability and increased apoptosis of AEC II significantly in concentration-dependent manner embodied in increased caspase-3 expression and the activity of caspase-3. Simultaneously, our results also indicated that LPS inhibited surfactant protein-C (SP-C) expression in AEC II. Mechanistic studies revealed that LPS treatment significantly increased the expression of NF-κB p50, NF-κB p65 and IKKβ proteins as well as induced IκB-α phosphorylation. Moreover, pretreatment with IKK inhibitor IKK-16 or NF-κB inhibitor PDTC ameliorated LPS-caused alterations in cleaved caspase-3 expression, the activity of caspase-3 and SP-C expression. Taken together, these results demonstrate that LPS can induce apoptosis of AEC II and decrease SP-C expression partly through activating the NF-κB pathway.
脂多糖（LPS）是革兰氏阴性菌外膜的一种成分，是脓毒症休克的主要病因之一。在此，我们研究LPS诱导的大鼠肺泡II型上皮细胞（AEC II）凋亡以及LPS对AEC II中表面活性蛋白C（SP-C）表达的影响，以及可能的分子机制。LPS暴露以浓度依赖的方式显著损害AEC II的细胞活力并增加其凋亡，表现为caspase-3表达增加和caspase-3活性增强。同时，我们的结果还表明LPS抑制AEC II中表面活性蛋白C（SP-C）的表达。机制研究表明，LPS处理显著增加NF-κB p50、NF-κB p65和IKKβ蛋白的表达，并诱导IκB-α磷酸化。此外，用IKK抑制剂IKK-16或NF-κB抑制剂PDTC预处理可改善LPS引起的裂解型caspase-3表达、caspase-3活性和SP-C表达的改变。综上所述，这些结果表明LPS可诱导AEC II凋亡并部分通过激活NF-κB途径降低SP-C表达。
