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Dig Liver Dis. 2014 May;46(5):433-9. doi: 10.1016/j.dld.2014.01.156. Epub 2014 Feb 26.

Lack of interleukin-1α in Kupffer cells attenuates liver inflammation and expression of inflammatory cytokines in hypercholesterolaemic mice.

Author information

1
The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel Hashomer, Israel.
2
Pathology Department, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel.
3
Department of Microbiology and Immunology, Ben Gurion University, Beer Sheva, Israel.
4
The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel.
5
The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Israel. Electronic address: yehuda.kamari@sheba.health.gov.il.

Abstract

BACKGROUND:

The role of Kupffer cell interleukin (IL)-1 in non-alcoholic steatohepatitis development remains unclear.

AIMS:

To evaluate the role of Kupffer cell IL-1α, IL-1β or IL-1 receptor type-1 (IL-1R1) in steatohepatitis.

METHODS:

C57BL/6 mice were irradiated and transplanted with bone marrow-derived cells from WT, IL-1α-/-, IL-1β-/- or IL-1R1-/- mice combined with Kupffer cell ablation with Gadolinium Chloride, and fed atherogenic diet. Plasma and liver triglycerides and cholesterol, serum alanine aminotransferase (ALT), liver histology and expression levels of inflammatory genes were assessed.

RESULTS:

The ablation and replacement of Kupffer cells with bone marrow-derived cells was confirmed. The atherogenic diet elevated plasma and liver cholesterol, reduced plasma and liver triglycerides and increased serum ALT levels in all groups. Steatosis and steatohepatitis were induced, but without liver fibrosis. A reduction in the severity of portal inflammation was observed only in mice with Kupffer cell deficiency of IL-1α. Accordingly, liver mRNA levels of inflammatory genes encoding for IL-1α, IL-1β, TNFα, SAA1 and IL-6 were significantly lower in mice with Kupffer cell deficiency of IL-1α compared to WT mice.

CONCLUSION:

Selective deficiency of IL-1α in Kupffer cells reduces liver inflammation and expression of inflammatory cytokines, which may implicate Kupffer cell-derived IL-1α in steatohepatitis development.

KEYWORDS:

Cytokine; Fatty liver; IL-1; Inflammation; Kupffer cells; NASH

PMID:
24582082
DOI:
10.1016/j.dld.2014.01.156
[Indexed for MEDLINE]

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