LXA4 stimulates ZO-1 expression and transepithelial electrical resistance in human airway epithelial (16HBE14o-) cells.
Lipoxin A(4) (LXA(4)) is a biologically active eicosanoid produced in human airways that displays anti-inflammatory properties. In cystic fibrosis and severe asthma, LXA(4) production has been reported to be decreased, and, in such diseases, one of the consequences of airway inflammation is disruption of the tight junctions. In the present study, we investigated the possible role of LXA(4) on tight junction formation, using transepithelial electrical resistance (TER) measurements, Western blotting, and immunofluorescence. We observed that exposure to LXA(4) (100 nM) for 2 days significantly increased zonula occludens-1 (ZO-1), claudin-1, and occludin expression at the plasma membrane of confluent human bronchial epithelial 16HBE14o- cells. LXA(4) (100 nM) stimulated the daily increase of the 16HBE14o- cell monolayer TER, and this effect was inhibited by boc-2 (LXA(4) receptor antagonist). LXA(4) also had a rapid effect on ZO-1 immunofluorescence at the plasma membrane and increased TER within 10 min. In conclusion, our experiments provide evidence that LXA(4) plays certainly a new role for the regulation of tight junction formation and stimulation of the localization and expression of ZO-1 at the plasma membrane through a mechanism involving the LXA(4) receptor.
Institut National de la Santé et de la Recherche Médicale U454, Centre Hospitalier Universitaire Arnaud de Villeneuve, Montpellier, France.
Yael
Y
Grumbach
Nga Vu Thi
NV
Quynh
Raphaël
R
Chiron
Valérie
V
Urbach
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002461:Cell Line, Transformed; D017097:Electric Impedance; D005455:Fluorescent Antibody Technique; D006801:Humans; D044045:Lipoxins / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism*; D018613:Microscopy, Confocal; D010750:Phosphoproteins / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D019108:Tight Junctions / Q000187:drug effects* / Q000502:physiology; D062826:Zonula Occludens-1 Protein
D000894:Anti-Inflammatory Agents, Non-Steroidal; D044045:Lipoxins; D008565:Membrane Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; C040527:lipoxin A4; D011493:Protein Kinase C