Protein phosphatase 2A activation attenuates inflammation in murine models of acute lung injury

The objective of this study was to determine whether PP2A regulated this response in vivo by investigating the impact of pharmacologic activation of PP2A on chemokine production and activation of the MAPK cascade and lung injury using endotoxin- and bacterial-challenge models of ARDS in mice. N6-cyclopentyladenosine (N6-CPA) increased PP2A activity and inhibited endotoxin-induced cytokine production in a murine alveolar macrophage cell line. N6-CPA pretreatment in mice challenged with intratracheal endotoxin decreased chemokine production, reduced neutrophil infiltration, and attenuated lung injury. Following initiation of lung injury with live Pseudomonas aeruginosa, mice that received N6-CPA 4 h following bacterial challenge showed attenuated chemokine production and reduced neutrophil infiltration compared with control mice. Pharmacologic PP2A activation both limited and prevented inflammation and tissue injury in two direct injury models of ARDS. These results suggest modulation of PP2A activity as a therapeutic target in ARDS.

Source: AJP: Lung Cellular and Molecular Physiology - October 31, 2016 Category: Respiratory Medicine Authors: McHugh, W. M., Russell, W. W., Fleszar, A. J., Rodenhouse, P. E., Rietberg, S. P., Sun, L., Shanley, T. P., Cornell, T. T. Tags: ARTICLES Source Type: research