https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://nova.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 ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51927 Wed 07 Feb 2024 15:00:03 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23093 Thu 28 Oct 2021 13:04:03 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26728 Thu 24 Mar 2022 11:33:42 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21995 Fri 25 May 2018 17:44:00 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25080 Fri 01 Apr 2022 09:27:01 AEDT ]]> https://nova.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.]]> Fri 01 Apr 2022 09:21:01 AEDT ]]>