Cyclooxygenase and cytokine regulation in lung fibroblasts activated with viral versus bacterial pathogen associated molecular patterns

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• 作者：William R. Wright ; Nicholas S. Kirkby ; Neil A. Galloway-Phillipps ; Daniel M. Reed ; Mark J. Paul-Clark ; Jane A. Mitchell
• 关键词：Cyclooxygenase ; Lung fibroblast ; TLR ; IL-8 ; IP-10 ; PGE2
• 刊名：Prostaglandins and Other Lipid Mediators
• 出版年：December, 2013
• 年：2013
• 卷：107
• 期：Complete
• 页码：4-12
• 全文大小：1555 K

文摘

Cyclooxygenase (COX) is required for prostanoid (e.g. prostaglandin PGE₂) production. Constitutive COX-1 and inducible COX-2 are implicated in lung diseases, such as idiopathic pulmonary fibrosis (IPF). Using lung fibroblasts from humans and wild type, COX-1^{鈭?鈭?/sup> and COX-2鈭?鈭?/sup> mice, we investigated how COX activity modulates cell growth and inflammatory responses induced by activators of Toll-like receptors (TLRs) 1-8. In mouse tissue, PGE₂ release from fresh lung was COX-1 driven, in lung in culture (24 h) COX-1 and COX-2 driven, and from proliferating lung fibroblasts exclusively COX-2 driven. COX-2 limited proliferation in lung fibroblasts and both isoforms limited KC release induced by a range of TLR agonists. Less effect of COX was seen on TLR-induced IP-10 release. In human lung fibroblasts inhibition of COX with diclofenac was associated with increased release of IL-8 and IP-10. Our results may have implications for the treatment of IPF.}