TY - JOUR T1 - Late-breaking abstract: α-1 antitrypsin activates protein phosphatase 2A (PP2A) to counter lung inflammatory responses JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P875 AU - Patrick Geraghty AU - Edward Eden AU - Manju Pillai AU - Michael Campos AU - Noel McElvaney AU - Robert Foronjy Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P875.abstract N2 - This study investigated whether α-1 antitrypsin (A1AT) acts via protein phosphatase 2A (PP2A), a key serine threonine phosphatase, to alter TNF signaling, inflammation and proteolytic responses in the lung. PP2A activity was measured in peripheral blood neutrophils from A1AT deficient (PiZZ) and healthy (PiMM) individuals. PP2A activation was assessed in human neutrophils, airway epithelial cells and peripheral blood monocytes treated with plasma purified A1AT protein. PP2A was silenced in lung epithelial cells treated with A1AT and MMP and cytokine production was then measured following TNF-α stimulation. We found that neutrophils from PiZZ subjects had significantly lower PP2A activity. A1AT activated PP2A in several cell types in the lung.Moreover, A1AT acted via PP2A to prevent p38 and IκBα phosphorylation in TNF-α stimulated epithelial cells.In addition, A1AT modulated PP2A activity to counter MMP and cytokine expression triggered by TNF signaling in the lung. Thus, these findings establish for the first time that A1AT acts via PP2A to exert potent anti-inflammatory effects in the lung. ER -