| First Author | Wang YY | Year | 2019 |
| Journal | Biochem Biophys Res Commun | Volume | 517 |
| Issue | 4 | Pages | 741-748 |
| PubMed ID | 31400857 | Mgi Jnum | J:291228 |
| Mgi Id | MGI:6443403 | Doi | 10.1016/j.bbrc.2019.07.125 |
| Citation | Wang YY, et al. (2019) Sting is a critical regulator of spinal cord injury by regulating microglial inflammation via interacting with TBK1 in mice. Biochem Biophys Res Commun 517(4):741-748 |
| abstractText | Spinal cord injury (SCI) is a devastating neurological condition that results in progressive tissue loss, secondary to vascular dysfunction and inflammation. Lack of effective pharmacotherapies for SCI is mainly attributable to an incomplete understanding of its pathogenesis. Stimulator of interferon gene (Sting), also known as Transmembrane protein 173 (TMEM173), activates the type I interferon-regulated innate immune response, playing crucial role in modulating inflammation. However, the mechanism underlying Sting activation in SCI is still unclear. Here, we reported that Sting functioned as a positive regulator of SCI. Sting expression was increased in the injured spinal cord samples of SCI mice, along with significantly up-regulated levels of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta and IL-6. Suppressing Sting expression in lipopolysaccharide-incubated mouse microglia markedly reduced the activation of nuclear factor-kappaB (NF-kappaB) and mitogen activated protein kinases (MAPKs) signaling pathways, as illustrated by the decreased phosphorylation of IKKbeta, IkappaBalpha, NF-kappaB/p65, p38, ERK1/2 and JNK. Furthermore, LPS-stimulated release of pro-inflammatory cytokines in microglial cells was also reversed by Sting knockdown. In contrast, LPS-induced inflammation was further accelerated in microglial cells with Sting over-expression through potentiating NF-kappaB and MAPKs signaling. Mechanistically, Sting directly interacted with the TANK-binding kinase 1 (TBK1), thus promoting its phosphorylation and the activation of down-streaming NF-kappaB and MAPKs signaling pathways. Notably, the effects of Sting on SCI progression were verified in mice. Consistently, Sting knockout alleviated inflammatory response and facilitated recovery after SPI in mice through blocking TBK1 activation and subsequent NF-kappaB and MAPKs phosphorylation. In summary, our findings may provide a novel strategy for prevention and treatment of SCI by targeting Sting. |
