| First Author | Spittau B | Year | 2013 |
| Journal | Glia | Volume | 61 |
| Issue | 2 | Pages | 287-300 |
| PubMed ID | 23065670 | Mgi Jnum | J:191135 |
| Mgi Id | MGI:5461095 | Doi | 10.1002/glia.22435 |
| Citation | Spittau B, et al. (2013) Endogenous transforming growth factor-beta promotes quiescence of primary microglia in vitro. Glia 61(2):287-300 |
| abstractText | Microglia are the immune cells of the central nervous system (CNS) and play important roles under physiological and pathophysiological conditions. Activation of microglia has been reported for a variety of CNS diseases and is believed to be involved in inflammation-mediated neurodegeneration. Loss of TGFbeta1 results in increased microgliosis and neurodegeneration in mice which indicates that TGFbeta1 is an important regulator of microglial functions in vivo. Here, we addressed the role of endogenous TGFbeta signaling for microglia in vitro. We clearly demonstrate active TGFbeta signaling in primary microglia and further introduce Klf10 as a new TGFbeta target gene in microglia. Moreover, we provide evidence that microglia express and release TGFbeta1 that acts in an autocrine manner to activate microglial TGFbeta/Smad signaling in vitro. Using microarrays, we identified TGFbeta-regulated genes in microglia that are involved in TGFbeta1 processing, its extracellular storage as well as activation of latent TGFbeta. Finally, we demonstrate that pharmacological inhibition of microglial TGFbeta signaling resulted in upregulation of the proinflammatory markers IL6 and iNOS and downregulation of the alternative activation markers Arg1 and Ym1 in vitro. Together, these data clearly show that endogenous TGFbeta1 and autocrine TGFbeta signaling is important for microglial quiescence in vitro and further suggest the upregulation of TGFbeta1 in neurodegenerative diseases as a mechanism to regulate microglia functions and silence neuroinflammation. (c) 2012 Wiley Periodicals, Inc. |
