Protectin D1 and maresin 1 attenuate airway hyperreactivity induced by IL‐13 in human isolated small bronchi

Background and Purpose Interleukin (IL)‐13 is implicated in airway hyperreactivity (AHR), a key feature of asthma. We explored the potential anti‐AHR activity of selected specialised pro‐resolving mediators (SPMs) in IL‐13‐induced AHR models, using human bronchial smooth muscle cells (BSMCs) and human isolated bronchi. Experimental Approach Calcium flux responses induced by histamine or LTD 4 were assessed in BSMCs preconditioned with IL‐13 and SPMs for 24 h. Human bronchi were isolated from lung tissue and preconditioned for 48 h in the presence or absence of IL‐13 and SPMs. Concentration‐response relationships for histamine and LTD 4 were established using myography to determine efficacy ( E max ) and potency (pEC 50 ) following interventions. Key Results In BSMCs, exposure to IL‐13 increased calcium flux ( E max ) triggered by histamine and LTD 4 . Protectin D1 (PD1) and maresin 1 (MaR1) reversed this effect, but not lipoxin A 4 , resolvin D2, and maresin‐conjugate in tissue repair 3 (MCTR3). In bronchi, IL‐13 exposure amplified contractions to histamine and LTD 4 , and this enhancement was reversed by PD1 and MaR1. In contrast, PD1 and MaR1 added acutely during myography had no effect on agonist‐induced contractility. PD1 attenuated IL‐13–induced enhancement of airway contractions triggered by mast cell activation. CysLT 1 antagonism did not influence the anti‐hyperreactive effect of SPMs. Chemo‐informatics revealed structural similarities between PD1 and MaR1 that may explain the anti‐hyperreactive action of these two SPMs. Conclusion and Implications This new anti‐hyperreactive action of PD1 and MaR1 encourages further research into their potential as therapies for the treatment of airway hyperreactivity.