Role of IRAK-M in Alcohol Induced Liver Injury

Wang, Yipeng; Hu, Youjia; Chao, Chen; Yuksel, Muhammed; Colle, Isabelle; Flavell, Richard A.; Ma, Yun; Yan, Huiping; Wen, Li
February 2013
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
Academic Journal
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.


Related Articles

  • Association Pattern of Interleukin-1 Receptor-Associated Kinase-4 Gene Polymorphisms with Allergic Rhinitis in a Han Chinese Population. Yuan Zhang; Xiaoping Lin; Desrosiers, Martin; Wei Zhang; Na Meng; Zhao, Liping; Han, Demin; Luo Zhang // PLoS ONE;2011, Vol. 6 Issue 6, p1 

    Objective: Interleukin-1 receptor-associated kinase-4 (IRAK-4) encodes a kinase that is essential for NF-kB activation in Tolllike receptor and T-cell receptor signaling pathways, indicating a possible crosstalk between innate and acquired immunities. We attempted to determine whether the...

  • Clinical Snippets.  // Journal of Investigative Dermatology;Feb2015, Vol. 135 Issue 2, p328 

    An introduction is presented in which the author discusses several articles within the issue on topics including defective transmembrane ectodysplasin A signaling effect on hair follicle, Toll-like receptor in pathogenesis of contact dermatitis and Ultraviolet radiation induced immunosuppression.

  • Neurodegeneration: Neurodegeneration takes its TOLL. Lewis, Sian // Nature Reviews Neuroscience;Jun2015, Vol. 16 Issue 6, p316 

    The article discusses a research on the impact of Toll-interleukin receptor (TIR) in the loss of NAD+ used for neurodegeneration, which references the study "SARM1 activation triggers axon degeneration locally via NAD+ destruction by J. Gerdst and colleagues in the 2015 issue.

  • IN THIS ISSUE.  // International Immunology;Aug2011, Vol. 23 Issue 8, pNP 

    No abstract available.

  • TLR7 inhibition. Eigenbrod, Tatjana; Dalpke, Alexander H. // JAK-STAT;Jan-Mar2013, Vol. 2 Issue 1, p1 

    The article discusses the findings of a study which describes the role of Toll-like receptors 7 (TLR7) in the development and progression of pancreatic cancer. The researchers have demonstrated the inhibition of TLR7 in cell cyle regulation and activation of multiple cell signaling pathways...

  • Endotoxin Tolerance Induced by Lipopolysaccharides Derived from Porphyromonas gingivalis and Escherichia coli: Alternations in Toll-Like Receptor 2 and 4 Signaling Pathway. Sun, Ying; Li, Hui; Sun, Meng-Jun; Zheng, Yang-Yu; Gong, Dan-Jun; Xu, Yan // Inflammation;Feb2014, Vol. 37 Issue 1, p268 

    Periodontitis is a chronic inflammatory disease induced by bacteria. Exposure of the host to periodontal pathogens and their virulence factors induces a hyporesponsive state to subsequent challenge, which is termed endotoxin tolerance. In this experiment, we studied the cytokine production in...

  • A new role for downstream Toll-like receptor signaling in mediating immediate early gene expression during focal cerebral ischemia. Famakin, Bolanle M; Mou, Yongshan; Johnson, Kory; Spatz, Maria; Hallenbeck, John // Journal of Cerebral Blood Flow & Metabolism;Feb2014, Vol. 34 Issue 2, p258 

    To better understand the role of downstream Toll-like receptor (TLR) signaling during acute cerebral ischemia, we performed cDNA microarrays, on brain RNA, and cytokine arrays, on serum, from wild type (WT), MyD88−/− and TRIF-mutant mice, at baseline and following permanent middle...

  • Upregulated genes in toll-like receptor (TLR) signaling pathway in periodontitis-affected gingival tissues. Abe, Daisuke; Kubota, Takehiko; Morozumi, Toshiya; Yoshie, Hiromasa // Open Journal of Stomatology;Jan2014, Vol. 4 Issue 1, p22 

    Toll-like receptor (TLR) signaling is thought to be one of the most important pathways initiating periodontitis onset. We have previously reported that the TLR signaling pathway is upregulated in periodontitis- affected gingival tissues by microarray pathway frequency analysis. The aim of the...

  • Pellino-1 in microglia. Dempsey, Laurie A // Nature Immunology;Jun2013, Vol. 14 Issue 6, p535 

    No abstract available.


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics