https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 The phosphorylated form of FTY720 activates PP2A, represses inflammation and is devoid of S1P agonism in A549 lung epithelial cells https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:26728 Wed 11 Apr 2018 17:31:36 AEST ]]> Basal protein phosphatase 2A activity restrains cytokine expression: role for MAPKs and tristetraprolin https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28327 in vitro we show that inhibition of basal PP2A activity by okadaic acid (OA) releases restraint on MAPKs and thereby increases MAPK-mediated pro-asthmatic cytokines, including IL-6 and IL-8. Notably, PP2A inhibition also impacts on the anti-inflammatory protein – tristetraprolin (TTP), a destabilizing RNA binding protein regulated at multiple levels by p38 MAPK. Although PP2A inhibition increases TTP mRNA expression, resultant TTP protein builds up in the hyperphosphorylated inactive form. Thus, when PP2A activity is repressed, pro-inflammatory cytokines increase and anti-inflammatory proteins are rendered inactive. Importantly, these effects can be reversed by the PP2A activators FTY720 and AAL(s), or more specifically by overexpression of the PP2A catalytic subunit (PP2A-C). Moreover, PP2A plays an important role in cytokine expression in cells stimulated with TNFα; as inhibition of PP2A with OA or PP2A-C siRNA results in significant increases in cytokine production. Collectively, these data reveal the molecular mechanisms of PP2A regulation and highlight the potential of boosting the power of endogenous phosphatases as novel anti-inflammatory strategies to combat asthmatic inflammation.]]> Wed 11 Apr 2018 13:50:35 AEST ]]> Theophylline represses IL-8 secretion from airway smooth muscle cells independently of phosphodiesterase inhibition: novel role as a protein phosphatase 2A activator https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25564 ex vivo and in vivo models of respiratory disease. Thus, our study is the first to link theophylline with PP2A activation as a novel mechanism to control respiratory inflammation.]]> Sat 24 Mar 2018 07:35:18 AEDT ]]> TLR2 ligation induces corticosteroid insensitivity in A549 lung epithelial cells: anti-inflammatory impact of PP2A activators https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:25080 Sat 24 Mar 2018 07:15:04 AEDT ]]> Activating protein phosphatase 2A (PP2A) enhances tristetraprolin (TTP) anti-inflammatory function in A549 lung epithelial cells https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:23093 Sat 24 Mar 2018 07:12:30 AEDT ]]> Activiating protein phosphatase 2A (PP2A) enhances tristetraprolin (TTP) anti-inflammatory function in A549 lung epithelial cells https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21995 Fri 25 May 2018 17:44:00 AEST ]]>