| First Author | Liu J | Year | 2017 |
| Journal | FEBS J | Volume | 284 |
| Issue | 24 | Pages | 4200-4215 |
| PubMed ID | 29052963 | Mgi Jnum | J:271928 |
| Mgi Id | MGI:6282314 | Doi | 10.1111/febs.14294 |
| Citation | Liu J, et al. (2017) Deficiency of p38alpha in macrophage ameliorates d-galactosamine/TNF-alpha-induced acute liver injury in mice. FEBS J 284(24):4200-4215 |
| abstractText | Growing evidence suggests that hepatic macrophages play an important role in tissue repair after liver injury by coordinating the induction and resolution of inflammation, removing apoptotic cells, and promoting hepatocyte proliferation. Understanding the role of macrophages in the pathogenesis of liver injury will help pave the way to future therapeutics. Here, we investigated whether macrophage p38alpha plays a regulatory role in the tissue repair following d-galactosamine (GalN)/tumor necrosis factor-alpha (TNF-alpha)-induced acute liver injury. We found that macrophage p38alpha-deficient mice displayed decreased mortality and relieved liver injury as evident from less apoptosis, accelerated regeneration, decreased granulocytes recruitment, monocytes infiltration, and cytokine production after GalN/TNF-alpha treatment. Mechanistically, we found that p38 signaling was activated by lipopolysaccharide/interferon-gamma treatment but not by inteleukin-4 stimulation, while pharmaceutical inhibition of p38alpha induced a shift in polarization from M1 macrophages to M2 macrophages. Together, our results indicated that macrophage p38alpha signaling is involved in the pathogenesis of liver injury induced by GalN/TNF-alpha, and inhibition of p38alpha signaling in macrophage could ameliorate liver injury and accelerate regeneration, probably by promoting the polarization of macrophages from the M1 phenotype to the M2 phenotype. |
