title: Cytokine profiles, signalling pathways and effects of fluticasone propionate in respiratory syncytial virus-infected human foetal lung fibroblasts.
abstract: To examine cytokine production in response to RSV infection, we assessed the levels of 29 cytokines released from RSV-infected human foetal lung fibroblasts. We also examined the relationships between the effects of fluticasone propionate and various signalling pathways in the cells. Twenty-four hours after infection (1MOI), RSV-infected cells released cytokines, for example proinflammatory cytokines (IL-1β, IL-6 and TNF-α), anti-inflammatory (IL-1ra), Th1 (IFN-γ, IFN-λ1a, IL-2 and IL-12), Th2 (IL-4, IL-5, IL-10 and IL-13), granulopoiesis-inducing (G-CSF and GM-CSF), eosinophil recruitment-inducing (eotaxin and RANTES) and neutrophil recruitment-inducing cytokines (IL-8, IP-10, MCP-1 and MIP-1α). Aberrant release of most was significantly suppressed by fluticasone propionate. Twelve hours after RSV infection, increased phosphorylation of Akt, p38 MAPK, ERK1/2 and IκB-α was noted. Fluticasone propionate suppressed the phosphorylation of Akt, p38 MAPK, and ERK1/2, but not IκB-α, in virus-infected cells. TLR-4 expression was unchanged in control and RSV-infected cells, and TLR-3 and RIG-I expression was not detected. The results indicate that RSV infection induces aberrant production and release of certain cytokines through these signalling pathways in human lung fibroblasts. Overproduction and imbalance of these cytokines may be associated with the pathophysiology of RSV-induced excessive and allergic inflammation.
authors: Department of Surgery, Institute of Medical Sciences, Kyorin University, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan.
authors: Erina
authors: E
authors: Seki
authors: Masakazu
authors: M
authors: Yoshizumi
authors: Ryota
authors: R
authors: Tanaka
authors: Akihide
authors: A
authors: Ryo
authors: Taisei
authors: T
authors: Ishioka
authors: Hiroyuki
authors: H
authors: Tsukagoshi
authors: Kunihisa
authors: K
authors: Kozawa
authors: Yoshimichi
authors: Y
authors: Okayama
authors: Junko
authors: J
authors: Okabe-Kado
authors: Tomoyuki
authors: T
authors: Goya
authors: Hirokazu
authors: H
authors: Kimura
mesh_terms: D000730:Androstadienes / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D000068298:Fluticasone; D054884:Host-Pathogen Interactions; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008168:Lung / Q000166:cytology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012136:Respiratory Syncytial Viruses / Q000502:physiology*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins; D051193:Toll-Like Receptors; D000068298:Fluticasone
keywords: cytokine; fluticasone propionate; human foetal lung fibroblast; respiratory syncytial virus; signalling pathway