| First Author | Zhao H | Year | 2018 |
| Journal | Mol Immunol | Volume | 101 |
| Pages | 303-311 | PubMed ID | 30032072 |
| Mgi Jnum | J:325300 | Mgi Id | MGI:6859992 |
| Doi | 10.1016/j.molimm.2018.07.021 | Citation | Zhao H, et al. (2018) HMBOX1 in hepatocytes attenuates LPS/D-GalN-induced liver injury by inhibiting macrophage infiltration and activation. Mol Immunol 101:303-311 |
| abstractText | The HMBOX1 (Homeobox Containing 1) gene was first isolated from the human pancreatic cDNA libraries and is widely expressed in many tissues. Previously, we detected high expression of HMBOX1 in the liver, but its function was unclear. In this study, hepatocyte-specific HMBOX1 knockout mice (Hm( big up tri, openhep) mice) were generated and used to characterize the function of HMBOX1 in the LPS/D-GalN-induced acute liver failure model. HMBOX1-knockout exhibits exacerbated liver injury induced by LPS/D-GalN, accompanied with high levels of inflammatory cytokines both in the liver and in circulation. Further investigation demonstrated that HMBOX1 negatively regulates NF-kappaB signal transduction. Therefore, HMBOX1-knockout in hepatocytes promotes CCL2 expression through the activation of NF-kappaB signaling, which enhanced the infiltration of macrophages into the liver. In addition, the decrease of HMBOX1 in hepatocytes promotes the activation of macrophages, upregulating CD80 and MHC, as well as inflammatory factors TNF-alpha and IL-6. Importantly, overexpression of HMBOX1 rescued liver injury in Hm( big up tri, openhep) mice. These findings indicate that HMBOX1 in hepatocytes acts as a key immunosuppressive factor for inflammation and plays a critical protective role in LPS/D-GalN-induced liver injury. |
