Deletion of tumor progression locus two attenuates alcoholinduced

Alcoholic liver disease (ALD) is the predominant cause of liver-related morbidity and mortality. Inflammatory cytokines, such as tumor necrosis factor-α and interferon-γ, inducing liver injury and lead to the development of ALD. The clinical manifestations are nausea, vomiting and jaundice, also lead to liver enlargement and painful, meanwhile, can be complicated by liver failure and upper gastrointestinal bleeding. Alcoholic hepatitis has a high independent risk of death more than inactive cirrhosis. A group of liver biopsy study found that the best prognosis of these patients is fatty liver, the 4–5 years of survival rate is 70% to 80%. The worst prognosis is alcoholic cirrhosis with alcoholic hepatitis patients, whose 4–5 years survival rate is 30% to 50%. And the prognosis of alcoholic hepatitis or cirrhosis patients is between the two, 4 to 5 years survival rate is 50% to 75% (1). The exact molecular mechanisms of the injury have not been elucidated yet. Tumor progression locus 2 (Tpl2) is a potent inflammatory mediator of serine/threonine protein kinase that regulates Th1 differentiation, drives the production of TNFα, and defense against intracellular pathogens of Toxoplasma gondii, listeria monocytogenes and mycobacterium tuberculosis (2). Tpl2 is closely related to tumor cell transformation and is overexpressed in lung cancer, breast cancer, endometrial carcinoma and colon cancer (3). However, there is relatively little known on the contribution of Tpl2 to ALD. In this manuscript, Dr. Camilla P. Stice et al. used TPL2KO mice to create alcohol-fed mouse model and then explore the role of TPL2 in it. They found that liver Tpl2 mRNA expression in the EtOH diet WT mice was significantly increased, and in the same time, indicated that the absence of TPL2 showed significant reductions in inflammatory cytokines, TNF alpha, IL-6 and IL-1 beta, and macrophage marker F4/80, reducing the number of inflammatory foci in the liver. Besides, they showed TPL2 deletion reduces hepatic steatosis and effect on phosphorylation of ERK and JNK, but neither of them reached statistical significance