LXA₄stimulates ZO-1 expression and transepithelial electrical resistance in human airway epithelial (16HBE14o-) cells

Abstract

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.

Human Mesenchymal Stem (Stromal) Cells Promote the Resolution of Acute Lung Injury in Part through Lipoxin A4

“…Additionally, LXA 4 inhibits neutrophil transepithelial migration (33) and airway epithelial proinflammatory mediator expression in an ALX/FPR2-dependent manner (33,34). LXA 4 also displays mucosal protection by stimulating ZO-1 expression and transepithelial electrical resistance in human airway epithelial cells (35). Moreover, LXA 4 activates the alveolar epithelial cell basolateral sodium channel, Na,K-ATPase, and increases alveolar fluid clearance in rats (36), and interestingly MSCs increase alveolar fluid clearance in endotoxin-injured The degree of lung injury (atelectasis, alveolar and interstitial inflammation, alveolar and interstitial hemorrhage, alveolar and interstitial edema, necrosis, and overdistension) in six sections from the lower lobes using the following criteria: 0, no injury; 1, injury to 25% of the field; 2, injury to 50% of the field; 3, injury to 75% of the field; 4, diffuse injury.…”

Lipoxin A4 Counter-regulates Histamine-stimulated Glycoconjugate Secretion in Conjunctival Goblet Cells

“…In human neutrophils, ALX/FPR2 activation leads to lipid remodeling, arachidonic acid release, and activation of phospholipase D (PLD) via PKC with a small increase in [Ca 2+ ] i 35. LXA 4 had no effect on [Ca 2+ ] i 36 in human astrocytoma cells while it increased [Ca 2+ ] i , in human bronchial epithelia as well as increased the number of tight junctions and Cl − secretion and decreased Na + absorption373839. Thus LXA 4 can have variable effects on [Ca 2+ ] i and other cell functions and cellular responses to LXA 4 need to be determined for each cell type.…”

Reduced 15-lipoxygenase 2 and lipoxin A4/leukotriene B4ratio in children with cystic fibrosis

“…Mice treated with analogues of LXA 4 and subsequently challenged with Pseudomonas aeruginosa contained the bacterial challenge more effectively [14]. LXA 4 augments airway epithelial innate defence by stimulating tight junction formation [15], enhancing calcium-activated chloride secretion [16], and by restoration of airway surface liquid height in CF airway epithelial cells [17]. LXA 4 concentration in CF bronchoalveolar lavage (BAL) has been variously reported as significantly suppressed or not significantly different from controls [14,18].…”