1. PTP1B promotes macrophage activation by regulating the NF-κB pathway in alcoholic liver injury
- Author
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Ying-Yin Sun, Lei Yang, Fang-Tian Bu, Na-Na Yin, Cheng Huang, Xiao-Sa Du, Jun Li, Yaru Liu, and Hai-xia Yu
- Subjects
Lipopolysaccharides ,Male ,0301 basic medicine ,Inflammation ,Toxicology ,Proinflammatory cytokine ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Fibrosis ,medicine ,Animals ,Macrophage ,Gene silencing ,Liver Diseases, Alcoholic ,Protein Tyrosine Phosphatase, Non-Receptor Type 1 ,Liver injury ,Ethanol ,business.industry ,NF-kappa B ,Central Nervous System Depressants ,NF-κB ,General Medicine ,Macrophage Activation ,medicine.disease ,Up-Regulation ,Mice, Inbred C57BL ,RAW 264.7 Cells ,030104 developmental biology ,Liver ,chemistry ,Cancer research ,Cytokines ,Steatohepatitis ,medicine.symptom ,business ,hormones, hormone substitutes, and hormone antagonists ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
Alcoholic liver injury (ALI) is a part of alcohol-related liver diseases. These diseases include steatohepatitis, alcoholic fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Accumulating data indicates that alcohol metabolism and circulating endotoxin/lipopolysaccharide (LPS) contribute to macrophage activation, which leads to the development of ALI. Protein tyrosine phosphatase 1B (PTP1B) has been shown to be involved in many tissue inflammations as well as liver fibrosis; however, the role of PTP1B in ALI is still unclear. In this study, PTP1B expression was elevated in liver tissues and primary macrophages isolated from EtOH-fed mice. Moreover, PTP1B expression was elevated in RAW264.7 cells stimulated with alcohol and LPS. Additional studies showed that silencing of PTP1B reduced the inflammatory response and expression of inflammatory cytokines such as IL-1β, IL-6 and TNF-α, while overexpression of PTP1B induced inflammation in RAW264.7 cells. In addition, we found that NF-κB pathway was activated in RAW264.7 cells stimulated with alcohol and LPS, and PTP1B silencing or overexpression could regulate NF-κB signaling. In conclusion, this study revealed the function of PTP1B in ALI via its regulation of the NF-κB signaling pathway and may provide theoretical support for further research on ALI.
- Published
- 2020
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