Rapamycin Attenuates Pulmonary Allergic Vasculitis in Murine Model by Reducing TGF-β Production in the Lung

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Author(s)

    • Koizumi Rumi
    • Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine
    • Sasaki Nobuhito
    • Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine
    • Nakamura Yutaka
    • Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine
    • Suzuki Naomi
    • Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine
    • Sawai Takashi
    • Department of Pathology, Iwate Medical University School of Medicine
    • Yamauchi Kohei
    • Division of Pulmonary Medicine, Allergy and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine

Abstract

<b>Background:</b> Rapamycin has been reported to inhibit mesenchymal cell proliferation in a murine model of pulmonary fibrosis. In the present study, we examined the effects of rapamycin on vascular remodeling including intraluminal myofibroblast proliferation in a murine model of allergic vasculitis with eosinophil infiltration.<br> <b>Methods:</b> C57BL/6 mice were sensitized with ovalbumin (OVA) and alum. The positive controls were exposed to aerosolized OVA daily for 7 days. The other group of mice was administered with rapamycin (1mg/kg) intraperitoneally, in parallel with daily exposure to aerosolized OVA for 7 days. On the 3<sup>rd</sup> and 7<sup>th</sup> day, bronchoalveolar lavage (BAL) was performed and the lungs were excised for pathological analysis. Cell differentials were determined and concentrations of IL-4, IL-5, IL-13 and TGF-β in the BAL fluid (BALF) were measured. Semi-quantitative analysis of pathological changes in the pulmonary arteries was evaluated according to the severity of vasculitis.<br> <b>Results:</b> The number of eosinophils in BALF was reduced significantly in the mice treated with rapamycin compared to the positive control. There was a significant decrease in the TGF-β concentration of the BALF in the rapamycin-treated group compared to that of the positive control. The pathological scores were reduced significantly in the rapamycin-treated group compared to the positive control group. Intraluminal myofibroblasts in pulmonary arteries were reduced dramatically in the rapamycin-treated group compared to the positive control group.<br> <b>Conclusions:</b> Rapamycin suppressed pulmonary vascular remodeling in a murine model of allergic vasculitis with eosinophil infiltration through reducing eosinophil infiltration and TGF-β production in the lung and inhibition against biological action of TGF-β.<br>

Journal

  • Allergology International

    Allergology International 63(3), 457-466, 2014

    Japanese Society of Allergology

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