| Autor: |
Shota Mizunoe, Tsuyoshi Shuto, Shingo Suzuki, Chizuru Matsumoto, Kenji Watanabe, Keiko Ueno-Shuto, Mary Ann Suico, Kouhei Onuki, Dieter C. Gruenert, Hirofumi Kai |
| Jazyk: |
angličtina |
| Rok vydání: |
2012 |
| Předmět: |
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| Zdroj: |
Journal of Pharmacological Sciences, Vol 118, Iss 4, Pp 512-520 (2012) |
| Druh dokumentu: |
article |
| ISSN: |
1347-8613 |
| DOI: |
10.1254/jphs.11240FP |
| Popis: |
Cystic fibrosis (CF) is the most common lethal inherited disorder and is caused by mutations in the gene encoding the CF transmembrane regulator (CFTR). The CF lung expresses a profound proinflammatory phenotype that appears to be related to a constitutive hypersecretion of interleukin (IL)-8 from airway epithelial cells in response to microbial infection. Since overproduction of IL-8 in CF contributes to massive bronchial infiltrates of neutrophils, identification of the pathways underlying IL-8 induction could provide novel drug targets for treatment of neutrophil-dominated inflammatory diseases such as CF. Here, we show that IL-17A synergistically increases IL-8 production induced by a toll-like receptor (TLR) 2 agonist, peptidoglycan (PGN), or TLR4 agonist, lipopolysaccharide (LPS), in a human CF bronchial epithelial cell line (CFBE41o-). A strong synergism was also observed in primary human CF bronchial epithelial cells, but not in human non-CF cell lines and primary cells. Notably, despite the induction of nuclear factor-κB and MAP kinases during TLR2 or TLR4 activation in CFBE41o-, IL-17A-dependent synergism appears to be the result of enhanced PGN- or LPS-induced phosphorylation of p38. Taken together, these studies provide evidence that IL-17A is a critical factor in increasing IL-8 expression in bacteria-infected CF airways via a pathway that regulates p38 phosphorylation. Keywords:: interleukin (IL)-17, toll-like receptor 2 and 4 (TLR2/TLR4), IL-8, cystic fibrosis (CF), p38 |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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