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

L. Karra, O. Haworth, R. Priluck, B. D. Levy, F. Levi-Schaffer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Chronic mucosal inflammation is the hallmark of important and common airway diseases, such as allergic rhinitis (AR) and asthma. Lipoxin A 4 (LXA 4) is an endogenous pro-resolving mediator for mucosal inflammation that decreases allergic and asthmatic responses. Lipoxin B 4 (LXB 4) is a structurally distinct member of the lipoxin family that signals in a manner distinct from LXA 4. LXB 4 is generated by mucosal tissues, but its actions in allergic inflammation are unknown. Here, we used murine models of AR and asthma to investigate LXB 4 's activity in mucosal inflammation. In the upper airway, LXB 4 significantly decreased nasal mucosal leukocytes and degranulation of mast cells (MCs) and eosinophils. In the lower airway, LXB 4 significantly decreased airway inflammation, mucus metaplasia, and hyper-responsiveness. Inhibition of MC degranulation in vivo by LXB 4 was more potent than dexamethasone, and these agents displayed unique profiles for cytokine regulation; however, their overall anti-inflammatory actions were comparable. LXB 4 decreased eotaxin-dependent eosinophil chemotaxis, IgE-mediated MC degranulation, and expression of type 2 cytokine receptors. Together, these findings indicate that LXB 4 carries cell type selective and mucosal protective actions that broaden the lipoxin family's therapeutic potential for upper and lower airway catabasis.

Original languageAmerican English
Pages (from-to)852-862
Number of pages11
JournalMucosal Immunology
Volume8
Issue number4
DOIs
StatePublished - 25 Jul 2015

Bibliographical note

Funding Information:
We acknowledge Professor Charles N. Serhan for helpful discussions on this project and critical appraisal of the manuscript, as well as Nour Karra and Jennifer Colby for assisting with sample preparations. This research was supported in part by the US National Institutes of Health grants AI068084, HL68669, and P01-GM095467 (B.D.L.) and by the Aimwell Charitable Fund, UK (F.L-S).

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