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Bacterial flagellin‐induced IL‐8 expression via lipid raft formation and activation of PKC and MAP kinases in A549
Author(s) -
Im Jintaek,
Cho Min Kyung,
Yun CheolHeui,
Han Seung Hyun
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.543
Subject(s) - flagellin , a549 cell , microbiology and biotechnology , chemistry , kinase , protein kinase c , transcription factor , biology , receptor , biochemistry , cell , gene
In the lung, alveolar type II epithelial cells recognize pathogen‐associated molecular pattern and secret chemokines to initiate innate immunity. Here, we investigated the mechanism for the induction of a chemokine, IL‐8, by bacterial flagellins, from Salmonella typhimurium and Bacillus subtilis , in a human alveolar type II epithelial cell‐line, A549. Both flagellins induced expressions of IL‐8 protein and mRNA in dose‐ and time‐dependent manners. The IL‐8 expression was inhibited by nystatin (a lipid raft inhibitor) but not by chlorpromazine (a clathrin‐coated pits inhibitor). Interestingly, toll‐like receptor 5, a receptor for flagellin, was found in the intracellular compartment rather than the cell surface. The IL‐8 expression was attenuated by inhibitors for PKC or MAP kinases whereas no inhibitory effect was observed by inhibitors for reactive oxygen species, PI3kinase, or PKA. Furthermore, treatment of A549 with flagellin enhanced the DNA binding activity of transcription factors, NF‐κB and NF‐IL6 that are involved in the transcription of IL‐8 gene. Collectively, these results suggest that flagellin‐induced IL‐8 expression requires formation of lipid rafts and activation of PKC and MAP kinases leading to the activation of transcription factors, NF‐κB and NF‐IL6 in human alveolar type II epithelial cells.