title: Ciclesonide inhibits TNFα- and IL-1β-induced monocyte chemotactic protein-1 (MCP-1/CCL2) secretion from human airway smooth muscle cells.
abstract: 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 β(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 β(2)-agonist) on MCP-1 production from human ASM cells. TNFα and IL-1β induced MCP-1 secretion from human ASM cells. Formoterol had no effect on MCP-1 expression, while ciclesonide significantly inhibited IL-1β- and TNFα-induced MCP-1. Furthermore, ciclesonide inhibited IL-1β- and TNFα-induced MCP-1 mRNA and IL-1β- and TNFα-induced MCP-1 promoter and enhancer luciferase reporters. Western blots showed that ciclesonide had no effect on IκB degradation. Finally, ciclesonide inhibited an NF-κB luciferase reporter. Our data show that ciclesonide inhibits IL-1β- and TNFα-induced MCP-1 production from human ASM cells via a transcriptional mechanism involving inhibition of NF-κB binding.
authors.affiliation: Division of Respiratory Medicine, Nottingham Respiratory Biomedical Research Unit, University of Nottingham, United Kingdom.
authors.forename: Jamie K
authors.initials: JK
authors.lastname: Patel
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Clifford
authors.forename: Karl
authors.initials: K
authors.lastname: Deacon
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Knox
mesh_terms: D018926:Anti-Allergic Agents / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000494:pharmacology; D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000378:metabolism*; D004983:Ethanolamines / Q000494:pharmacology; D000068759:Formoterol Fumarate; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011282:Pregnenediones / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D018926:Anti-Allergic Agents; D001993:Bronchodilator Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D004983:Ethanolamines; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D011282:Pregnenediones; D014409:Tumor Necrosis Factor-alpha; C120481:ciclesonide; D000068759:Formoterol Fumarate