Pretreatment with zinc protects Kupffer cells following administration of microbial products - 30/05/20
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Graphical abstract |
Kupffer cells (KCs) and hepatic stellate cells (HSCs) can respond to bacterial stimulation and cause increased secretion of LDH and thromboxane (TX) A2, and ultimately promote the process of liver fibrosis. Pretreatment with zinc sulfate solution can significantly reduce TXA2 secreted by KCs through Myd88-related pathways, which may serve as a new antibacterial weapon in patients with chronic liver diseases.
Le texte complet de cet article est disponible en PDF.Highlights |
• | Low serum zinc levels in patients with chronic liver disease are associated with more severe infections and fibrosis. |
• | Bacterial isolates significantly increased LDH levels in KCs and HSCs but had no effect on SECs. |
• | Zinc pretreatment instead of posttreatment showed a protective effect in KCs. |
Abstract |
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.
Le texte complet de cet article est disponible en PDF.Abbreviations : CLD, HSC, KC, PAMP, PMA, SBP, SEC
Keywords : Primary non-parenchymal cell, Spontaneous bacterial peritonitis, Zinc
Plan
Vol 127
Article 110208- juillet 2020 Retour au numéro
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