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Mucosal Immunol. 2015 Jul;8(4):852-62. doi: 10.1038/mi.2014.116. Epub 2014 Dec 3.

Lipoxin B₄ promotes the resolution of allergic inflammation in the upper and lower airways of mice.

Author information

1
Pharmacology Unit, The Institute for Drug Research, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
2
Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Abstract

Chronic mucosal inflammation is the hallmark of important and common airway diseases, such as allergic rhinitis (AR) and asthma. Lipoxin A4 (LXA4) is an endogenous pro-resolving mediator for mucosal inflammation that decreases allergic and asthmatic responses. Lipoxin B4 (LXB4) is a structurally distinct member of the lipoxin family that signals in a manner distinct from LXA4. LXB4 is generated by mucosal tissues, but its actions in allergic inflammation are unknown. Here, we used murine models of AR and asthma to investigate LXB4's activity in mucosal inflammation. In the upper airway, LXB4 significantly decreased nasal mucosal leukocytes and degranulation of mast cells (MCs) and eosinophils. In the lower airway, LXB4 significantly decreased airway inflammation, mucus metaplasia, and hyper-responsiveness. Inhibition of MC degranulation in vivo by LXB4 was more potent than dexamethasone, and these agents displayed unique profiles for cytokine regulation; however, their overall anti-inflammatory actions were comparable. LXB4 decreased eotaxin-dependent eosinophil chemotaxis, IgE-mediated MC degranulation, and expression of type 2 cytokine receptors. Together, these findings indicate that LXB4 carries cell type selective and mucosal protective actions that broaden the lipoxin family's therapeutic potential for upper and lower airway catabasis.

PMID:
25465102
PMCID:
PMC4454640
DOI:
10.1038/mi.2014.116
[Indexed for MEDLINE]
Free PMC Article

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