IL-19 Contributes to the Development of Nonalcoholic Steatohepatitis by Altering Lipid Metabolism

Abstract

Interleukin (IL)-19, a member of the IL-10 family, is an anti-inflammatory cytokine produced primarily by macrophages. Nonalcoholic steatohepatitis (NASH) is a disease that has progressed from nonalcoholic fatty liver disease (NAFLD) and is characterized by inflammation and fibrosis. We evaluated the functions of IL-19 in a NAFLD/NASH mouse model using a 60% high fat diet with 0.1% methionine, without choline, and with 2% cholesterol (CDAHFD). Wild-type (WT) and IL-19 gene-deficient (KO) mice were fed a CDAHFD or standard diet for 9 weeks. Liver injury, inflammation, and fibrosis induced by CDAHFD were significantly worse in IL-19 KO mice than in WT mice. IL-6, TNF-α, and TGF-β were significantly higher in IL-19 KO mice than in WT mice. As a mechanism using an in vitro experiment, palmitate-induced triglyceride and cholesterol contents were decreased by the addition of IL-19 in HepG2 cells. Furthermore, addition of IL-19 decreased the expression of fatty acid synthesis-related enzymes and increased ATP content in HepG2 cells. The action of IL-19 in vitro suppressed lipid metabolism. In conclusion, IL-19 may play an important role in the development of steatosis and fibrosis by directly regulating liver metabolism and may be a potential target for the treatment of liver diseases.

Gene-gene and gene-environment interactions of the inflammatory gene variants in the development of chronic obstructive pulmonary disease

“…The A allele of IL19 (rs2243193) was observed in the majority of gene-gene interaction patterns associated with low COPD risk in smokers together with C allele of IL4 (rs2243250) and T allele of PPBP (rs352010). IL19 is released by macrophages and monocytes after their activation by extracellular pathogens [35] . IL19, IL20, and IL24 genes are located at chromosome 1q32.1, and are IL10 family genes [14,15,35] .…”

“…IL19 is released by macrophages and monocytes after their activation by extracellular pathogens [35] . IL19, IL20, and IL24 genes are located at chromosome 1q32.1, and are IL10 family genes [14,15,35] . Upregulation of the IL19 results in the reduction of the inflammatory response by suppressing the expression of TNFA, IL6, and IL12 [14,15,35] .…”

“…IL19, IL20, and IL24 genes are located at chromosome 1q32.1, and are IL10 family genes [14,15,35] . Upregulation of the IL19 results in the reduction of the inflammatory response by suppressing the expression of TNFA, IL6, and IL12 [14,15,35] . Rong et al showed that increased serum levels of IL19 were correlated with COPD progression [36] .…”

“…Association of IL24 (rs291107) with COPD in nonsmokers has been observed. IL24 codes for one of the members of the IL10 family cytokines [14,15,35] . The major T allele of IL24 (rs291107) was a key component of the two…”

Transplantation of chemically-induced liver progenitor cells ameliorates hepatic fibrosis in mice with diet-induced nonalcoholic steatohepatitis

“…CDAHFD model that reproduces the pathophysiology of NASH, 6-week-old CB17/Icr-Prkdc <scid>/CrlCrlj mice (Charles River Laboratories Japan, Yokohama, Japan) were prepared and fed with a choline-deficient, l -amino acid-defined, high-fat diet (CDAHFD) (A06071302; Research Diets, Inc.) [ 19 ]. To clarify sufficient duration of feeding CDAHFD for establishing sufficient fibrosis, an area of hepatic fibrosis was evaluated by measuring positive area with Azan staining in 10 random fields (x1000) of view per individual using an image analysis software program (Win ROOF, MITANI Co., Tokyo, Japan) at 6, 8 and 12 weeks.…”