Premium
Regulation of ion transport and ASL height by the anti‐inflammatory mediator, lipoxin A4 in normal and cystic fibrosis bronchial epithelium
Author(s) -
Urbach Valerie,
Higgins Gerard,
Al-Alawai Mazen,
Costello Richard W,
McNally Paul,
Verriere Valia,
Harvey Brian J
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.696.9
Subject(s) - lipoxin , amiloride , cystic fibrosis , chemistry , respiratory epithelium , cystic fibrosis transmembrane conductance regulator , inflammation , extracellular , mucociliary clearance , ion transporter , transepithelial potential difference , secretion , epithelium , biophysics , endocrinology , medicine , receptor , biochemistry , biology , lung , pathology , sodium , membrane , organic chemistry
Mutations of CFTR results in defective Cl − secretion and Na + hyperabsorption which contributes to a reduction of the airway surface liquid layer height (ASLh) thus promoting bacterial colonization and inflammation. Lipoxin A 4 (LXA 4 ) which plays a central role in resolving inflammation is decreased in cystic fibrosis (CF). We have investigated the role of LXA 4 in modulating ion transport and ASLh in CF and non‐CF bronchial epithelial cell lines (CuFi‐1 and Nuli‐1) and primary cultures grown under an air‐liquid interface. ASLh were measured using confocal microscopy and ion transport using electrophysiological techniques. LXA 4 (1nM) significantly increased ASLh in CF and non‐CF epithelia. This effect was inhibited by bumetanide, amiloride, Boc‐2 (FPR2 antagonist), extracellular hexokinase, reactive blue 2 and NF340 (P2Y and P2Y11 receptor antagonist). LXA 4 stimulated a carbenoxolone (Panexin‐1 inhibitor)‐sensitive apical ATP release, intracellular Ca 2+ mobilization and Cl − secretion and inhibited Na + absorption. These effects of LXA 4 involving apical ATP release, inhibition of Na + absorption and stimulation of Cl − secretion to enhance ASL dynamics open up a new therapeutic avenue to promote mucociliary clearance in CF airways.