| First Author | Chang CP | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 12 | Pages | e28323 |
| PubMed ID | 22163006 | Mgi Jnum | J:182269 |
| Mgi Id | MGI:5315080 | Doi | 10.1371/journal.pone.0028323 |
| Citation | Chang CP, et al. (2011) Concanavalin A/IFN-gamma triggers autophagy-related necrotic hepatocyte death through IRGM1-mediated lysosomal membrane disruption. PLoS One 6(12):e28323 |
| abstractText | Interferon-gamma (IFN-gamma), a potent Th1 cytokine with multiple biological functions, can induce autophagy to enhance the clearance of the invading microorganism or cause cell death. We have reported that Concanavalin A (Con A) can cause autophagic cell death in hepatocytes and induce both T cell-dependent and -independent acute hepatitis in immunocompetent and immunodeficient mice, respectively. Although IFN-gamma is known to enhance liver injury in Con A-induced hepatitis, its role in autophagy-related hepatocyte death is not clear. In this study we report that IFN-gamma can enhance Con A-induced autophagic flux and cell death in hepatoma cell lines. A necrotic cell death with increased lysosomal membrane permeabilization (LMP) is observed in Con A-treated hepatoma cells in the presence of IFN-gamma. Cathepsin B and L were released from lysosomes to cause cell death. Furthermore, IFN-gamma induces immunity related GTPase family M member 1(IRGM1) translocation to lysosomes and prolongs its activity in Con A-treated hepatoma cells. Knockdown of IRGM1 inhibits the IFN-gamma/Con A-induced LMP change and cell death. Furthermore, IFN-gamma(-/-) mice are resistant to Con A-induced autophagy-associated necrotic hepatocyte death. We conclude that IFN-gamma enhances Con A-induced autophagic flux and causes an IRGM1-dependent lysosome-mediated necrotic cell death in hepatocytes. |
