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Rapamycin inhibits IL-33-induced airway inflammation

Ananda Mirchandani, Robert Salmond, Foo Liew
European Respiratory Journal 2011 38: 4892; DOI:
Ananda Mirchandani
Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom
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Robert Salmond
Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom
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Foo Liew
Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom
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Abstract

Introduction: IL-33, a member of the IL-1 cytokine family, mediates a range of pathologies including asthma and arthritis (Liew F.Y. et al. Nature Reviews Immunology, 2010; 10: 103-110). The mechanism by which IL-33 induces airway inflammation and the associated signalling pathways are incompletely understood. Rapamycin was initially described as a macrolide antibiotic that selectively blocks the mammalian target of rapamycin (mTOR), a serine/threonine kinase involved in numerous signaling pathways.

Aim: To identify the role of mTOR and rapamycin in IL-33-mediated airway inflammation.

Method: BALB/c mice were treated intranasally with 1 μg IL-33 daily with or without 1mg/kg rapamycin for 5 days. Airway inflammation was assessed on day 6 by bronchoalveolar lavage (BAL) cellularity and cytokine analysis.

Results: Intranasal IL-33 induced profound airway inflammation with increased cellular recruitment on BAL consisting mainly of macrophages and eosinophils. Treatment with rapamycin significantly reduced IL-33-mediated cellular recruitment (Figure 1A) and reduced both eosinophil (Figure 1B) and macrophage (Fig. 1C) influx into the airway.

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Rapamycin also significantly reduced IL-33-mediated IL-5 and IL-13 production in BAL fluid.

Conclusions: Intranasal IL-33 induces airway inflammation that is partially blocked by treatment with intranasal rapamycin suggesting an important role for mTOR in the signaling pathway of IL-33 in vivo.

  • © 2011 ERS
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Rapamycin inhibits IL-33-induced airway inflammation
Ananda Mirchandani, Robert Salmond, Foo Liew
European Respiratory Journal Sep 2011, 38 (Suppl 55) 4892;

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Rapamycin inhibits IL-33-induced airway inflammation
Ananda Mirchandani, Robert Salmond, Foo Liew
European Respiratory Journal Sep 2011, 38 (Suppl 55) 4892;
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