title: Role of IRAK-M in alcohol induced liver injury.
abstract: Increasing evidence suggests that innate immunity plays an important role in alcohol-induced liver injury and most studies have focused on positive regulation of innate immunity. The main objective of this study was to investigate the negative regulator of innate immunity, IL-1/Toll-like receptor (TLR) signaling pathways and interleukin receptor-associated kinase-M (IRAK-M) in alcoholic liver injury. We established an alcohol-induced liver injury model using wild type and IRAK-M deficient B6 mice and investigated the possible mechanisms. We found that in the absence of IRAK-M, liver damage by alcohol was worse with higher alanine transaminase (ALT), more immune cell infiltration and increased numbers of IFNγ producing cells. We also found enhanced phagocytic activity in CD68(+) cells. Moreover, our results revealed altered gut bacteria after alcohol consumption and this was more striking in the absence of IRAK-M. Our study provides evidence that IRAK-M plays an important role in alcohol-induced liver injury and IRAK-M negatively regulates the innate and possibly the adaptive immune response in the liver reacting to acute insult by alcohol. In the absence of IRAK-M, the hosts developed worse liver injury, enhanced gut permeability and altered gut microbiota.
authors: The Sections of Endocrinology, Yale University School of Medicine, New Haven, CT, USA.
authors: Yipeng
authors: Y
authors: Wang
authors: Youjia
authors: Y
authors: Hu
authors: Chen
authors: C
authors: Chao
authors: Muhammed
authors: M
authors: Yuksel
authors: Isabelle
authors: I
authors: Colle
authors: Richard A
authors: RA
authors: Flavell
authors: Yun
authors: Y
authors: Ma
authors: Huiping
authors: H
authors: Yan
authors: Li
authors: L
authors: Wen
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D055106:Genome-Wide Association Study; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D008108:Liver Diseases, Alcoholic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054892:Metagenome; D051379:Mice; D018345:Mice, Knockout; D010539:Permeability; D010587:Phagocytosis / Q000276:immunology; D020161:Physical Chromosome Mapping; D020641:Polymorphism, Single Nucleotide; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D051858:Forkhead Transcription Factors; D007371:Interferon-gamma; D053592:Interleukin-1 Receptor-Associated Kinases; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C498833:Foxp3 protein, mouse; C507772:Irak3 protein, mouse