Novel insights into the role of LRRC8A in ameliorating alveolar fluid clearance in LPS induced acute lung injury.
Leucine-rich repeat-containing 8A (LRRC8A) protein was recently identified as an essential component of volume-regulated anion channel which plays a central role in maintaining cell volume. The aim of this study was to elucidate the role of LRRC8A in alveolar fluid clearance (AFC) and the effect of inflammatory cytokines on LRRC8A and the underlying mechanism. Lipopolysaccharide (LPS) was used to generate a rat acute lung injury model. The results showed that the concentrations of IL-1β, TNF-α and IL-6 in bronchoalveolar lavage fluid increased significantly, but the expression of LRRC8A in the lung tissue decreased dramatically in the acute lung injury group followed by a decline in the AFC rate. Additionally, LRRC8A knockdown reduced AFC in normal rats. However, specific overexpression of LRRC8A in the lung could increase AFC. Furthermore, we observed the effects of LPS, IL-1β, TNF-α and IL-6 on the LRRC8A current in alveolar type II (ATII) cells, and IL-1β showed the greatest inhibition among them, which was involved in phospho-p38 activation. Overall, LRRC8A plays an essential role in the progression of AFC in LPS-induced acute lung injury, and chronic treatment with IL-1β or TNF-α could inhibit the function of LRRC8A in ATII cells by targeting phospho-p38. All of the findings suggested that LRRC8A could be a new partner in AFC and a potential target for the treatment of acute lung injury.
['Zhang|Huiran|H|', 'Liu|Yani|Y|', 'Li|Honglin|H|', 'Li|Jingwen|J|', 'Luo|Yuan|Y|', 'Yan|Xixin|X|']
D055371:Acute Lung Injury D000818:Animals D018450:Disease Progression D005786:Gene Expression Regulation D053583:Interleukin-1beta D008070:Lipopolysaccharides D008297:Male D008565:Membrane Proteins D011650:Pulmonary Alveoli D051381:Rats D017207:Rats, Sprague-Dawley D048051:p38 Mitogen-Activated Protein Kinases
LRRC8A Alveolar fluid clearance Acute lung injury IL-1β p38