title: Toll-like receptor-mediated signaling cascade as a regulator of the inflammation network during alcoholic liver disease.
abstract: Chronic abuse of alcohol leads to various histological abnormalities in the liver. These are conditions collectively known as alcoholic liver disease (ALD). Currently, ALD is considered to be one of the major causes of death worldwide. An impaired intestinal barrier with related endotoxemia is among the various pathogenetic factors. This is mainly characterized by circulating levels of lipopolysaccharide (LPS), considered critical for the onset of intra-hepatic inflammation. This in turn promotes hepatocellular damage and fibrosis in ALD. Elevated levels of LPS exert their effects by binding to Toll-like receptors (TLRs) which are expressed by all liver-resident cells. The activation of TLR signaling triggers an overproduction and release of some cytokines, which promote an autocatalytic cascade of other pro-inflammatory signals. In this review, we provide an overview of the mechanisms that sustain LPS-mediated activation of TLR signaling, reporting current experimental and clinical evidence of its role during inflammation in ALD.
authors.affiliation: Sara Ceccarelli, Valerio Nobili, Anna Alisi, Hepato-Metabolic Disease Unit and Liver Research Unit, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Ceccarelli
authors.affiliation: Sara Ceccarelli, Valerio Nobili, Anna Alisi, Hepato-Metabolic Disease Unit and Liver Research Unit, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Nobili
authors.affiliation: Sara Ceccarelli, Valerio Nobili, Anna Alisi, Hepato-Metabolic Disease Unit and Liver Research Unit, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Alisi
mesh_terms: D000818:Animals; D018988:Bacterial Translocation; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators; D051193:Toll-Like Receptors
keywords: Alcoholic liver disease; Cirrhosis; Cytokines; Inflammation; Nuclear factor-κB; Toll-like receptors