TY - JOUR
T1 - Lack of interleukin-1α in Kupffer cells attenuates liver inflammation and expression of inflammatory cytokines in hypercholesterolaemic mice
AU - Olteanu, Sarita
AU - Kandel-Kfir, Michal
AU - Shaish, Aviv
AU - Almog, Tal
AU - Shemesh, Shay
AU - Barshack, Iris
AU - Apte, Ron N.
AU - Harats, Dror
AU - Kamari, Yehuda
N1 - Funding Information:
This study was supported in part by the Talpiot Sheba Medical Leadership grant (Yehuda Kamari).
PY - 2014/5
Y1 - 2014/5
N2 - 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.
AB - 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.
KW - Cytokine
KW - Fatty liver
KW - IL-1
KW - Inflammation
KW - Kupffer cells
KW - NASH
UR - http://www.scopus.com/inward/record.url?scp=84898879701&partnerID=8YFLogxK
U2 - 10.1016/j.dld.2014.01.156
DO - 10.1016/j.dld.2014.01.156
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C2 - 24582082
AN - SCOPUS:84898879701
SN - 1590-8658
VL - 46
SP - 433
EP - 439
JO - Digestive and Liver Disease
JF - Digestive and Liver Disease
IS - 5
ER -