Influence of polymorphisms in TNF-α and IL1β on susceptibility to alcohol induced liver diseases and therapeutic potential of miR-124-3p impeding TNF-α/IL1β mediated multi-cellular signaling in liver microenvironment

作者：Debanjali Dasgupta, Suchandrima Ghosh, Indrashish Dey, Swagata Majumdar, Saheli Chowdhury, Subhas Das, Sanjana Banerjee, Sanjana Banerjee, Mehelana Saha, Amit Kumar Ghosh, Neelanjana Roy, Alak Manna, Sukanta Ray, Shaleen Agarwal, Pradeep Bhaumik, Simanti Datta, Abhijit Chowdhury, Soma Banerjee, Soma Banerjee · 发表于：Frontiers in Immunology · 年份：2023 · DOI：10.3389/fimmu.2023.1241755 · 被引用次数：13 · 研究领域：Alcohol Consumption and Health Effects、Alcoholism and Thiamine Deficiency、Liver Disease Diagnosis and Treatment

Background and aims: Alcoholic liver disease (ALD) is the leading cause of the liver cirrhosis related death worldwide. Excessive alcohol consumption resulting enhanced gut permeability which trigger sensitization of inflammatory cells to bacterial endotoxins and induces secretion of cytokines, chemokines leading to activation of stellate cells, neutrophil infiltration and hepatocyte injury followed by steatohepatitis, fibrosis and cirrhosis. But all chronic alcoholics are not susceptible to ALD. This study investigated the causes of differential immune responses among ALD patients and alcoholic controls (ALC) to identify genetic risk factors and assessed the therapeutic potential of a microRNA, miR-124-3p. Materials and methods: Bio-Plex Pro™ Human Chemokine analysis/qRT-PCR array was used for identification of deregulated immune genes. Sequencing/luciferase assay/ELISA detected and confirmed the polymorphisms. THP1 co-cultured with HepG2/LX2/HUVEC and apoptosis assay/qRT-PCR/neutrophil migration assay were employed as required. Results: The combined data analysis of the GSE143318/Bio-Plex Pro™ Human Chemokine array and qRT-PCR array revealed that six genes (TNFα/IL1β/IL8/MCP1/IL6/TGFβ) were commonly overexpressed in both serum/liver tissue of ALD-patients compared to ALC. The promoter sequence analysis of these 6 genes among ALD (n=322)/ALC (n=168) samples revealed that only two SNPs, rs361525(G/A) at -238 in TNF-α/rs1143627(C/T) at -31 in IL1β were independently associated...