Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A4
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- 12 August 2002
- journal article
- Published by Springer Nature in Nature Medicine
- Vol. 8 (9) , 1018-1023
- https://doi.org/10.1038/nm748
Abstract
The prevalence of asthma continues to increase and its optimal treatment remains a challenge. Here, we investigated the actions of lipoxin A(4) (LXA(4)) and its leukocyte receptor in pulmonary inflammation using a murine model of asthma. Allergen challenge initiated airway biosynthesis of LXA(4) and increased expression of its receptor. Administration of a stable analog of LXA(4) blocked both airway hyper-responsiveness and pulmonary inflammation, as shown by decreased leukocytes and mediators, including interleukin-5, interleukin-13, eotaxin, prostanoids and cysteinyl leukotrienes. Moreover, transgenic expression of human LXA(4) receptors in murine leukocytes led to significant inhibition of pulmonary inflammation and eicosanoid-initiated eosinophil tissue infiltration. Inhibition of airway hyper-responsiveness and allergic airway inflammation with a stable LXA(4) analog highlights a unique counter-regulatory profile for the LXA(4) system and its leukocyte receptor in airway responses. Moreover, our findings suggest that lipoxin and related pathways offer novel multi-pronged therapeutic approaches for human asthma.Keywords
This publication has 34 references indexed in Scilit:
- The Th2 Lymphocyte Products IL-4 and IL-13 Rapidly Induce Airway Hyperresponsiveness Through Direct Effects on Resident Airway CellsAmerican Journal of Respiratory Cell and Molecular Biology, 2002
- Lipoxin-mediated inhibition of IL-12 production by DCs: a mechanism for regulation of microbial immunityNature Immunology, 2001
- Direct Effects of Interleukin-13 on Signaling Pathways for Physiological Responses in Cultured Human Airway Smooth Muscle CellsAmerican Journal of Respiratory and Critical Care Medicine, 2001
- Selectivity of Recombinant Human Leukotriene D4, Leukotriene B4, and Lipoxin A4 Receptors with Aspirin-Triggered 15-epi-LXA4 and Regulation of Vascular and Inflammatory ResponsesThe American Journal of Pathology, 2001
- Eosinophils generate brominating oxidants in allergen-induced asthmaJournal of Clinical Investigation, 2000
- Leukotriene B4 receptor transgenic mice reveal novel protective roles for lipoxins and aspirin-triggered lipoxins in reperfusionJournal of Clinical Investigation, 1999
- Interleukin-8 receptor modulates IgE production and B-cell expansion and trafficking in allergen-induced pulmonary inflammationJournal of Clinical Investigation, 1999
- Effects of lipoxin A4 on chemotaxis and degranulation of human eosinophils stimulated by platelet‐activating factor and N‐formyl‐L‐methionyl‐L‐leucyl‐L‐phenylalanineAllergy, 1994
- Cytokines in symptomatic asthma airwaysJournal of Allergy and Clinical Immunology, 1992
- Predominant TH2-like Bronchoalveolar T-Lymphocyte Population in Atopic AsthmaNew England Journal of Medicine, 1992