Microglial activation induced by the alarmin S100B is regulated by poly(ADP‐ribose) polymerase‐1. Issue 11 (22nd July 2016)

• Record Type: Journal Article
• Authors: Xu, Jianguo; Wang, Handong; Won, Seok Joon; Basu, Jayinee; Kapfhamer, David; Swanson, Raymond A.
• Is Part Of: Glia. Volume 64:Issue 11(2016:Nov.)
• Page Start: 1869
• Page End: 1878
• Publication Date: 2016-07-22
• Subjects: stroke -- trauma -- astrocyte -- PARP‐1 -- nitric oxide -- MMP9 -- veliparib; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.23026
• Languages: English
• ISSNs: 0894-1491

Abstract

Abstract : Brain injury resulting from stroke or trauma can be exacerbated by the release of proinflammatory cytokines, proteases, and reactive oxygen species by activated microglia. The microglial activation resulting from brain injury is mediated in part by alarmins, which are signaling molecules released from damaged cells. The nuclear enzyme poly(ADP‐ribose) polymerase‐1 (PARP‐1) has been shown to regulate microglial activation after brain injury, and here we show that signaling effects of the alarmin S100B are regulated by PARP‐1. S100B is a protein localized predominantly to astrocytes. Exogenous S100B added to primary microglial cultures induced a rapid change in microglial morphology, upregulation of IL‐1β, TNFα, and iNOS gene expression, and release of matrix metalloproteinase 9 and nitric oxide. Most, though not all of these effects were attenuated in PARP‐1 ‐/‐ microglia and in wild‐type microglia treated with the PARP inhibitor, veliparib. Microglial activation and gene expression changes induced by S100B injected directly into brain were likewise attenuated by PARP‐1 inhibition. The anti‐inflammatory effects of PARP‐1 inhibitors in acutely injured brain may thus be mediated in part through effects on S100B signaling pathways. GLIA 2016;64:1869–1878 Main Points: The astrocyte‐derived alarmin, S100B, is a potent and effective stimulus for microglial activation. This effect of S100B is mediated in part by poly(ADP‐ribose) polymerase‐1 (PARP‐1)