Phosphate Groups in the Lipid A Moiety Determine the Effects of LPS on Hepatic Stellate Cells: A Role for LPS-Dephosphorylating Activity in Liver Fibrosis

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RESEARCH PRODUCT

Phosphate Groups in the Lipid A Moiety Determine the Effects of LPS on Hepatic Stellate Cells: A Role for LPS-Dephosphorylating Activity in Liver Fibrosis

Yury Popov Jitske Langeland Eduard Post Leonie Beljaars Detlef Schuppan Detlef Schuppan Madhu S. Malo Madhu S. Malo Marlies Schippers Ilse Eichhorn Richard A. Hodin Klaas Poelstra José Luis Millán

subject

Lipopolysaccharides Liver Cirrhosis Male 0301 basic medicine medicine.medical_specialty Lipopolysaccharide Nitric Oxide Article Lipid A Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation Internal medicine medicine Animals Macrophage Phosphorylation lipid A lcsh:QH301-705.5 liver fibrosis Mice Inbred BALB C Interleukin-6 Macrophages lipopolysaccharide Biological activity General Medicine In vitro Rats Up-Regulation RAW 264.7 Cells 030104 developmental biology Endocrinology Liver chemistry lcsh:Biology (General)Hepatic stellate cell Alkaline phosphatase 030211 gastroenterology & hepatology lipids (amino acids peptides and proteins)hepatic stellate cells alkaline phosphatase

description

Alkaline phosphatase (AP) activity is highly upregulated in plasma during liver diseases. Previously, we demonstrated that AP is able to detoxify lipopolysaccharide (LPS) by dephosphorylating its lipid A moiety. Because a role of gut-derived LPS in liver fibrogenesis has become evident, we now examined the relevance of phosphate groups in the lipid A moiety in this process. The effects of mono-phosphoryl and di-phosphoryl lipid A (MPLA and DPLA, respectively) were studied in vitro and LPS-dephosphorylating activity was studied in normal and fibrotic mouse and human livers. The effects of intestinal AP were studied in mice with CCL4-induced liver fibrosis. DPLA strongly stimulated fibrogenic and inflammatory activities in primary rat hepatic stellate cells (rHSCs) and RAW264.7 macrophages with similar potency as full length LPS. However, MPLA did not affect any of the parameters. LPS-dephosphorylating activity was found in mouse and human livers and was strongly increased during fibrogenesis. Treatment of fibrotic mice with intravenous intestinal-AP significantly attenuated intrahepatic desmin+&minus

year	journal	country	edition	language
2020-12-17

10.3390/cells9122708 https://research.rug.nl/en/publications/a142ca28-aa35-4301-91f3-da7128303d3b