Loss of myeloid-specific protein phosphatase 2A enhances lung injury and fibrosis and results in IL-10 dependent sensitization of epithelial cell apoptosis.

Loss of myeloid-specific protein phosphatase 2A enhances lung injury and fibrosis and results in IL-10 dependent sensitization of epithelial cell apoptosis.
Am J Physiol Lung Cell Mol Physiol. 2019 Mar 06;:
Authors: Sun L, Hult EM, Cornell TT, Kim KK, Shanley TP, Wilke CA, Agarwal M, Gurcynski SJ, Moore BB, Dahmer MK
Abstract
Protein phosphatase 2A (PP2A), a ubiquitously expressed ser/thr phosphatase is an important regulator of cytokine signaling and cell function. We previously showed that myeloid-specific deletion of PP2A (LysMcrePP2A-/-) increased mortality in a murine peritoneal sepsis model. In the current study, we assessed the role of myeloid PP2A in regulation of lung injury induced by lipopolysaccharide (LPS) or bleomycin delivered intratracheally. LysMcrePP2A-/- mice experienced increased lung injury in response to both LPS and bleomycin. LysMcrePP2A-/- mice developed more exuberant fibrosis in response to bleomycin, elevated cytokine responses and chronic myeloid inflammation. Bone marrow derived macrophages (BMDMs) from LysMcrePP2A-/- mice showed exaggerated inflammatory cytokine release under conditions of both M1 and M2 activation. Notably, secretion of IL-10 was elevated under all stimulation conditions, including activation of BMDMs by multiple TLR ligands. Supernatants collected from LPS-stimulated LysMcrePP2A-/- BMDMs induced epithelial cell apoptosis in vitro, but this effect was mitigated when IL-10 was also depl...

Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - March 5, 2019 Category: Cytology Authors: Sun L, Hult EM, Cornell TT, Kim KK, Shanley TP, Wilke CA, Agarwal M, Gurcynski SJ, Moore BB, Dahmer MK Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research