Ciclesonide inhibits TNFα- and IL-1β-induced monocyte chemotactic protein-1 (MCP-1/CCL2) secretion from human airway smooth muscle cells

被引:24
作者
Patel, Jamie K.
Clifford, Rachel L.
Deacon, Karl
Knox, Alan J.
机构
[1] Univ Nottingham, Div Resp Med, Nottingham NG5 1PB, England
[2] Univ Nottingham, Nottingham Resp Biomed Res Unit, Nottingham NG5 1PB, England
基金
英国惠康基金;
关键词
glucocorticoid; nuclear factor-kappa B; inflammation; NF-KAPPA-B; CHEMOATTRACTANT PROTEIN-1; TRANSCRIPTIONAL REGULATION; GLUCOCORTICOID-RECEPTOR; CHRONIC-BRONCHITIS; GENE-EXPRESSION; RNA STABILITY; ASTHMA; RELEASE; MODULATION;
D O I
10.1152/ajplung.00257.2011
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Patel JK, Clifford RL, Deacon K, Knox AJ. Ciclesonide inhibits TNF alpha- and IL-1B-induced monocyte chemotactic protein-1 (MCP-1/CCL2) secretion from human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 302: L785-L792, 2012. First published January 13, 2012; doi: 10.1152/ajplung.00257.2011.-Monocyte chemotactic protein-1 (MCP-1) is a member of the CC family of cytokines. It has monocyte and lymphocyte chemotactic activity and stimulates histamine release from basophils. MCP-1 is implicated in the pathogenesis of inflammatory diseases, including asthma. The airway smooth muscle (ASM) layer is thickened in asthma, and the growth factors and cytokines secreted by ASM cells play a role in the inflammatory response of the bronchial wall. Glucocorticoids and beta(2)-agonists are first-line drug treatments for asthma. Little is known about the effect of asthma treatments on MCP-1 production from human ASM cells. Here, we determined the effect of ciclesonide (a glucocorticoid) and formoterol (a beta(2)-agonist) on MCP-1 production from human ASM cells. TNF alpha and IL-1 beta induced MCP-1 secretion from human ASM cells. Formoterol had no effect on MCP-1 expression, while ciclesonide significantly inhibited IL-1 beta- and TNF alpha-induced MCP-1. Furthermore, ciclesonide inhibited IL-1 beta- and TNF alpha-induced MCP-1 mRNA and IL-1 beta- and TNF alpha-induced MCP-1 promoter and enhancer luciferase reporters. Western blots showed that ciclesonide had no effect on I kappa B degradation. Finally, ciclesonide inhibited an NF-kappa B luciferase reporter. Our data show that ciclesonide inhibits IL-1 beta- and TNF alpha-induced MCP-1 production from human ASM cells via a transcriptional mechanism involving inhibition of NF-kappa B binding.
引用
收藏
页码:L785 / L792
页数:8
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