The CC motif chemokine ligand 11 contributes to alcoholic liver disease

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Life sciences Pub Date : 2025-01-20 DOI:10.1016/j.lfs.2025.123409

Jichen Li , Ben Wang , Shunjie Wang , Jieguo Wang , Anqi Zhou , Shanwen Gong , Yu Wang , Xiulian Miao , Yan Guo , Hao Wang , Hailong Ge

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引用次数: 0

Abstract

Aims

Alcoholic liver disease (ALD) is characterized by aberrant lipid metabolism and chronic inflammation that eventually give rise to cirrhosis and hepatocellular carcinoma. In the present study we investigated the contribution of CC motif chemokine ligand 11 (CCL11) to ALD pathogenesis.

Methods and materials

ALD was induced in mice by binge ethanol gavage or chronic ethanol feeding.

Key findings

Bioinformatic analysis of sequencing data indicated that CCL11 expression was up-regulated in hepatocytes from mice subjected to ethanol feeding compared to those from the control mice. Exposure to ethanol led to CCL11 up-regulation in primary murine hepatocytes in vitro. Consistently, Oil Red O (ORO) staining detected elevated lipid accumulation whereas quantitative PCR (qPCR) detected augmented expression of pro-inflammatory mediators in primary murine hepatocytes treated with recombinant CCL11. On the contrary, CCL11 knockout mice (KO) developed a less severe form of ALD compared to wild type littermates when subjected to either binge or chronic ethanol feeding. Finally, CCL11 antagonism by administration with an inhibitor to CCL11 receptor CCR3 (CCR3i) attenuated ALD in mice.

Significance

Our data support a role for CCL11 in ALD pathogenesis and provide proof-of-concept that targeting CCL11 can be considered as a therapeutic approach for ALD intervention.

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.