Pretreatment with zinc protects Kupffer cells following administration of microbial products
| Autor: | Hanwei Li, Christian J. Steib, Hao Lin, Jiang Zhang, Julia Mayerle, Tobias S. Schiergens, Andreas Wieser, Yuhui Fan, Alexander L. Gerbes |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Adult Liver Cirrhosis Male medicine.medical_specialty Bilirubin Kupffer Cells chemistry.chemical_element Zinc RM1-950 Chronic liver disease Systemic inflammation 03 medical and health sciences chemistry.chemical_compound Thromboxane A2 0302 clinical medicine Internal medicine medicine Hepatic Stellate Cells Spontaneous bacterial peritonitis Humans Aged Pharmacology Creatinine Liver Diseases Albumin Primary non-parenchymal cell General Medicine Middle Aged medicine.disease Zinc Sulfate 030104 developmental biology Endocrinology chemistry Gene Expression Regulation 030220 oncology & carcinogenesis Chronic Disease Hepatic stellate cell Female Therapeutics. Pharmacology medicine.symptom |
| Zdroj: | Biomedicine & Pharmacotherapy, Vol 127, Iss, Pp 110208-(2020) |
| ISSN: | 1950-6007 |
| Popis: | Background Systemic inflammation and severe fibrosis can reduce serum zinc levels, while zinc supplementation is reported to improve the prognosis of patients with chronic liver disease (CLD). Objectives We aimed to investigate the clinical application of serum zinc in patients with CLD and the anti-infective mechanism of zinc supplementation. Methods Based on the serum zinc level, 149 CLD patients were divided into 3 groups and their clinical parameters were compared. In in-vitro experiments, microbial isolates derived from patients were used to stimulate human liver non-parenchymal cells, and the zinc sulfate solution was added in certain experiments. The effect of zinc was compared by LDH and thromboxane A2 levels in the cell supernatant. Result Compared with other groups, patients with low serum zinc levels had significantly higher C-reactive protein (CRP), total bilirubin, INR, creatinine, and MELD scores, while albumin and GOT levels were reduced. Only CRP and albumin were significantly correlated with serum zinc in both low and normal-zinc groups. Bacterial isolates significantly increased LDH levels in Kupffer cells (KCs) and stellate cells but had no effect on sinusoidal endothelial cells, whereas zinc pretreatment protected KCs but not stellate cells. Thromboxane A2 secreted by KCs can also be induced by bacterial stimulation, accompanied by increased gene expression of Myd88, MAPK and NF-kB, while zinc pretreatment can attenuate that. Conclusion Serum zinc levels can be used to estimate infection and liver fibrosis in CLD patients. As a new antibacterial weapon, zinc supplementation acts on KCs through Myd88-MAPK related pathways. |
| Databáze: | OpenAIRE |
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