Overexpression of Tumor Necrosis Factor-Like Ligand 1 A in Myeloid Cells Aggravates Liver Fibrosis in Mice.
Jinbo GuoYuxin LuoFengrong YinXiaoxia HuoGuochao NiuMei SongShuang ChenXiao-Lan ZhangPublished in: Journal of immunology research (2019)
Macrophages are the master regulator of the dynamic fibrogenesis-fibrosis resolution paradigm. TNF-like ligand 1 aberrance (TL1A) was found to be able to induce intestinal inflammation and fibrosis. Furthermore, significantly increased TL1A had been detected in liver tissues and mononuclear cells of patients with primary biliary cirrhosis (PBC). This study was to investigate the effect of myeloid cells with constitutive TL1A expression on liver fibrogenesis. We found that TL1A expressions in liver tissues and macrophages were significantly increased in mice with liver fibrosis induced by injection of carbon tetrachloride (CCl4). TL1A overexpression in myeloid cells induced liver function injury, accelerated the necrosis and apoptosis of hepatocytes, recruited macrophages, and promoted activation of hepatic stellate cells (HSCs) and fibrosis. In vitro results of our study showed that TL1A overexpression in macrophages promoted secretion of platelet-derived growth factor-BB (PDGF-BB), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). Culturing macrophages with TL1A overexpression could accelerate the activation and proliferation of primary HSCs. These results indicated that constitutive TL1A expression in myeloid cells exacerbated liver fibrosis, probably through macrophage recruitment and secretion of proinflammatory and profibrotic cytokines.
Keyphrases
- liver fibrosis
- induced apoptosis
- cell cycle arrest
- growth factor
- oxidative stress
- endoplasmic reticulum stress
- rheumatoid arthritis
- cell death
- cell proliferation
- transcription factor
- gene expression
- bone marrow
- signaling pathway
- metabolic syndrome
- type diabetes
- insulin resistance
- immune response
- binding protein
- single molecule
- diabetic rats
- high fat diet induced
- long non coding rna
- endothelial cells