Peptidoglycan-mediated IL-8 expression in human alveolar type II epithelial cells requires lipid raft formation and MAPK activation

被引:31
作者
Cheon, In Su [1 ,2 ,3 ]
Woo, Sang Su [1 ]
Kang, Seok-Seong [1 ,2 ]
Im, Jintaek [1 ]
Yun, Cheol-Heui [4 ]
Chung, Dae Kyun [5 ,6 ]
Park, Dong Ki [7 ]
Han, Seung Hyun [1 ,2 ,3 ]
机构
[1] Seoul Natl Univ, Sch Dent, Dept Oral Microbiol & Immunol, Dent Res Inst, Seoul 110749, South Korea
[2] Seoul Natl Univ, Sch Dent, Program BK21, Seoul 110749, South Korea
[3] Int Vaccine Inst, Div Sci Lab, Seoul 151818, South Korea
[4] Seoul Natl Univ, Sch Agr Biotechnol, Seoul 151921, South Korea
[5] Kyung Hee Univ, Sch Biotechnol, Suwon 449701, South Korea
[6] Kyung Hee Univ, Inst Life Sci & Resources, Suwon 449701, South Korea
[7] Konkuk Univ, Dept Biosci & Biotechnol, Seoul 143701, South Korea
关键词
peptidoglycan; Staphylococcus aureus; IL-8; epithelial cells; a549; signaling; MAP kinase; transcription factor;
D O I
10.1016/j.molimm.2007.10.001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
Staphylococcus aureus, a major sepsis-causing Gram-positive bacterium, invades pulmonary epithelial cells and causes lung diseases. In the lung, alveolar type 11 epithelial cells play an important role in innate immunity by secreting chemokines and antimicrobial peptides upon bacterial infection whereas type I cells mainly function in gas-exchange. In this study, we investigated the ability of S. aureus peptidoglycan (PGN) to induce expression of a chemokine, IL-8, in a human alveolar type 11 epithelial cell line, A549. PGN induces IL-8 mRNA and protein expression in a dose- and time-dependent manner. Supplementation of soluble CD14 further enhanced the PGN-induced IL-8 expression. Interestingly, PGN-induced IL-8 expression was inhibited by nystatin, a specific inhibitor for lipid rafts, but not by chlorpromazine, a specific inhibitor for clathrin-coated pits. Furthermore, PGN-induced IL-8 expression was attenuated by inhibitors for MAP kinases such as ERK, p38 kinase, and JNK/SAPK, whereas no inhibitory effect was observed by inhibitors for reactive oxygen species or protein kinase C. Electrophoretic mobility shift assay demonstrates that PGN increased the DNA binding of the transcription factors, AP-1 and NF-kappa B while minimally, NF-IL6, all of which are involved in the transcription of IL-8. Taken together, these results suggest that PGN induces IL-8 expression in a CD 14-enhanced manner in human alveolar type 11 epithelial cells, through the formation of lipid rafts and the activation of MAP kinases, which ultimately leads to activation of AP-1, NF-kappa B, and NF-IL6. (c) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1665 / 1673
页数:9
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