Toll-like receptor 2-mediated sequential activation of MyD88 and MAPKs contributes to lipopolysaccharide-induced sp-a gene expression in human alveolar epithelial cells

Chi Yuan Chuang, Tyng-Guey Chen, Yu-Ting Tai, Ta-Liang Chen, Yu Hua Lin, Cheng Hsiu Tsai, Ruei-Ming Chen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Surfactant proteins (SPs) produced by pulmonary epithelial cells participate in the regulation of sepsis-induced acute lung injury. Our previous study has shown that lipopolysaccharide (LPS), a Gram-negative bacterial outer membrane component, can regulate sp-a gene expression in human lung carcinoma type II epithelial A549 cells. This study was further designed to evaluate the signal-transducing mechanisms of LPS-induced sp-a gene expression. Exposure of A549 cells to LPS induced SP-A mRNA and protein production in time-dependent manners. Application of toll-like receptor 2 (TLR2) siRNA into A549 cells decreased the levels of this receptor and simultaneously inhibited LPS-induced SP-A mRNA expression. Sequentially, LPS enhanced phosphorylation of mitogen-activated protein kinase (MEK) 4 and c-Jun NH2 terminal kinase 1 (JNK1) in time-dependent manners. Application of TLR2 siRNA decreased LPS-enhanced phosphorylation of MEK4 and JNK1. After knocking-down the translation of MyD88 by RNA interference, the LPS-triggered MEK4 phosphorylation was attenuated. Consequently, LPS augmented the translocation of c-Jun from the cytoplasm to nuclei without affecting c-Fos. Pretreatment of A549 cells with SP600125, an inhibitor of JNK1, significantly lowered LPS-induced SP-A mRNA production. Analyses of an electrophoretic mobility shift assay and a reporter gene further showed that LPS increased the transactivation activity of AP-1 in A549 cells. Therefore, the present study demonstrates that LPS can induce sp-a gene expression in human type II epithelial A549 cells through TLR2-mediated sequential activation of MyD88-MEK4-JNK1-AP-1.

Original languageEnglish
Pages (from-to)707-714
Number of pages8
JournalImmunobiology
Volume216
Issue number6
DOIs
Publication statusPublished - Jun 2011

Keywords

  • Acute lung injury
  • Alveolar epithelial cells
  • Lipopolysaccharide
  • MyD88-MEK4-JNK1-AP-1
  • Surfactant protein-A
  • Toll-like receptor 2

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

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