Lipoxin A4 has been described as a major signal for the resolution of inflammation and is abnormally produced in the lungs of\npatients with cystic fibrosis (CF). In CF, the loss of chloride transport caused by the mutation in the cystic fibrosis transmembrane\nconductance regulator (CFTR) Cl? channel gene results in dehydration,mucus plugging, and reduction of the airway surface liquid\nlayer (ASL) height which favour chronic lung infection and neutrophil based inflammation leading to progressive lung destruction\nand early death of people with CF. This review highlights the unique ability of LXA4 to restore airway surface hydration, to\nstimulate airway epithelial repair, and to antagonise the proinflammatory programof the CF airway, circumventing someof the most\ndifficult aspects of CF pathophysiology. The report points out novel aspects of the cellular mechanism involved in the physiological\nresponse to LXA4, including release of ATP fromairway epithelial cell via pannexin channel and subsequent activation of and P2Y11\npurinoreceptor. Therefore, inadequate endogenous LXA4 biosynthesis reported in CF exacerbates the ion transport abnormality\nand defective mucociliary clearance, in addition to impairing the resolution of inflammation, thus amplifying the vicious circle of\nairway dehydration, chronic infection, and inflammation.
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