Cytokine profiles, signalling pathways and effects of fluticasone propionate in respiratory syncytial virus-infected human foetal lung fibroblasts

Authors

  • Erina Seki,

    1. Department of Surgery, Institute of Medical Sciences, Kyorin University, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan
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  • Masakazu Yoshizumi,

    1. Gunma Prefectural Institute of Public Health and Environmental Sciences, 378 Kamioki-machi, Maebashi-shi, Gunma 371-0052, Japan
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  • Ryota Tanaka,

    1. Department of Surgery, Institute of Medical Sciences, Kyorin University, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan
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  • Akihide Ryo,

    1. Department of Molecular Biodefence Research, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan
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  • Taisei Ishioka,

    1. Gunma Prefectural Institute of Public Health and Environmental Sciences, 378 Kamioki-machi, Maebashi-shi, Gunma 371-0052, Japan
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  • Hiroyuki Tsukagoshi,

    1. Gunma Prefectural Institute of Public Health and Environmental Sciences, 378 Kamioki-machi, Maebashi-shi, Gunma 371-0052, Japan
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  • Kunihisa Kozawa,

    1. Gunma Prefectural Institute of Public Health and Environmental Sciences, 378 Kamioki-machi, Maebashi-shi, Gunma 371-0052, Japan
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  • Yoshimichi Okayama,

    1. Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, 30-1 Oyaguchi-kamimachi, Itabashi-ku, Tokyo 173-8610, Japan
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  • Junko Okabe-Kado,

    1. Research Institute for Clinical Oncology, Saitama Cancer Center, 818 Komuro, Ina-machi, Kita-adachi-gun, Saitama 362-0806, Japan
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  • Tomoyuki Goya,

    1. Department of Surgery, Institute of Medical Sciences, Kyorin University, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan
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  • Hirokazu Kimura

    Corresponding author
    1. Gunma Prefectural Institute of Public Health and Environmental Sciences, 378 Kamioki-machi, Maebashi-shi, Gunma 371-0052, Japan
    2. Infectious Disease Surveillance Center, National Institute of Infectious Diseases, 4-7-1Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan
    • Department of Surgery, Institute of Medical Sciences, Kyorin University, 6-20-2 Shinkawa, Mitaka-shi, Tokyo 181-8611, Japan
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Corresponding author: e-mail: kimhiro@nih.go.jp

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.

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