Subclinical-Dose Endotoxin Sustains Low-Grade Inflammation and Exacerbates Steatohepatitis in High-Fat Diet-Fed Mice
| Autor: | Shuo Geng, Honghui Guo, Na Diao, Mingsong Li, Ruoxi Yuan, Liwu Li, Keqiang Chen |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Lipopolysaccharides Male Neutrophils Apoptosis p38 Mitogen-Activated Protein Kinases Mice 0302 clinical medicine Non-alcoholic Fatty Liver Disease Immunology and Allergy Phosphorylation Mice Knockout Lipids Chemotaxis Leukocyte Liver Neutrophil Infiltration Knockout mouse Disease Progression Dual-Specificity Phosphatases 030211 gastroenterology & hepatology lipids (amino acids peptides and proteins) medicine.symptom medicine.medical_specialty MAP Kinase Signaling System p38 mitogen-activated protein kinases Immunology Inflammation Biology Diet High-Fat Models Biological Article 03 medical and health sciences Ballooning degeneration Apolipoproteins E Internal medicine medicine Animals Macrophages medicine.disease Lipid Metabolism Endotoxins Disease Models Animal 030104 developmental biology Endocrinology MAPK phosphatase Mitogen-Activated Protein Kinase Phosphatases Steatohepatitis |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 196(5) |
| ISSN: | 1550-6606 |
| Popis: | Subclinical circulating bacterial endotoxin LPS has been implicated as an important cofactor in the development and progression of nonalcoholic steatohepatitis, but the underlying mechanisms remain unclear. In this study, we demonstrated that 4-wk injection with superlow-dose LPS significantly promoted neutrophil infiltration and accelerated nonalcoholic steatohepatitis progression, including exacerbated macrovesicular steatosis, inflammation, and hepatocyte ballooning in high-fat diet–fed apolipoprotein E knockout mice. This effect could sustain for a month after stoppage of LPS injection. LPS also significantly increased numbers of apoptotic nuclei in hepatocytes and expressions of proapoptotic regulators. Moreover, LPS sustained the low-grade activation of p38 MAPK and inhibited the expression of the upstream MAPK phosphatase 7. By applying selective inhibitors, we demonstrated that the activation of p38 MAPKs is required for neutrophil migration induced by superlow-dose LPS in vitro. Together, these data suggest that superlow-dose LPS may sustain the low-grade activation of p38 MAPKs and neutrophil infiltration, leading to the exacerbation of steatohepatitis. |
| Databáze: | OpenAIRE |
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