Affiliation:
1. Beijing Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Capital Medical University, Beijing, China
2. Beijing Institute of Liver Diseases, Beijing, China
3. The Center for Growth, Metabolism and Aging, Sichuan University, Chengdu, China
Abstract
Acute-on-chronic liver failure (ACLF) carries a significant burden on critical care services and health care resources. However, the exact pathogenesis of ACLF remains to be elucidated, and novel treatments are desperately required. In our previous work, we utilized mice subjected to acute insult in the context of hepatic fibrosis to simulate the development of ACLF and documented the favorable hepatoprotection conferred by M2-like macrophages in vivo and in vitro. In the present study, we focused on the phenotypic switch of human and mouse macrophages and assessed the effects of this switch on apoptosis resistance in hepatocytes. For this purpose, human and mouse macrophages were isolated and polarized into M0, M(IFN-γ), M(IFN-γ→IL-4), M(IL-4) or M(IL-4→IFN-γ) subsets. Conditioned media (CM) from these subsets were applied to human and mouse hepatocytes followed by apoptosis induction. Cell apoptosis was evaluated by immunostaining for cleaved caspase-3. As a result, M(IFN-γ) or M(IL-4) macrophages switched their phenotype into M(IFN-γ→IL-4) or M(IL-4→IFN-γ) through reprogramming with IL-4 or IFN-γ, respectively. Importantly, hepatocytes pre-treated with M(IFN-γ→IL-4) CMs exhibited much weaker expression of cleaved caspase-3, compared to those pre-treated with M(IFN-γ) CM, and vice versa. Together, phenotypic switch of macrophages toward M(IL-4) phenotype confers hepatocytes enhanced resistance to apoptosis.
Funder
The National Key Research and Development Program of China
Digestive Medical Coordinated Development Center of Beijing Municipal Administration of Hospitals
Basic-Clinical Cooperation Project of Capital Medical University
National Science and Technology Key Project
Beijing Municipal Science & Technology Projects
Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support
YouAn fund for liver diseases and AIDS
Subject
Infectious Diseases,Cell Biology,Molecular Biology,Immunology,Microbiology
Cited by
7 articles.
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