Galectin-3 in Inflammasome Activation and Primary Biliary Cholangitis Development

Abstract

Primary biliary cholangitis (PBC) is a chronic inflammatory autoimmune liver disease characterized by inflammation and damage of small bile ducts. The NLRP3 inflammasome is a multimeric complex of proteins that after activation with various stimuli initiates an inflammatory process. Increasing data obtained from animal studies implicate the role of NLRP3 inflammasome in the pathogenesis of various diseases. Galectin-3 is a β-galactoside-binding lectin that plays important roles in various biological processes including cell proliferation, differentiation, transformation and apoptosis, pre-mRNA splicing, inflammation, fibrosis and host defense. The multilineage immune response at various stages of PBC development includes the involvement of Gal-3 in the pathogenesis of this disease. The role of Galectin-3 in the specific binding to NLRP3, and inflammasome activation in models of primary biliary cholangitis has been recently described. This review provides a brief pathogenesis of PBC and discusses the current knowledge about the role of Gal-3 in NLRP3 activation and PBC development.

Next-Generation Sequencing Analysis of Root Canal Microbiota Associated with a Severe Endodontic-Periodontal Lesion

“…Despite the bacterial etiology, tissue damage and inflammation are sustained and enhanced by the inflammatory host response with inflammatory mediators such as Galectin-3 (Gal-3), the Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and Interleukine-1. In particular, Gal-3 is implicated in the regulation of inflammation, as demonstrated in similar disease models [6][7][8].…”

“…A significant higher expression of Gal-3 is reported in inflammatory diseases such as periapical granulomas, radicular cysts, osteonecrosis of the jaw associated with bisphosphonates and periodontal diseases [29]. Additionally, Gal-3 activates the NLRP3 inflammasome [7,8], capable of converting pro-IL-1β to IL-1β, an important inflammatory mediator that participates in inflammatory processes and is implicated in periodontal tissue destruction [30]. Moreover, high expression of NLRP3 and IL-1β has been found in human gingival tissues with severe chronic periodontitis [31].…”

Deletion of RAGE fails to prevent hepatosteatosis in obese mice due to impairment of other AGEs receptors and detoxifying systems

“…Furthermore, Gal-3 has been previously involved in the activation of the NLRP3 inflammasome pathway, contributing to inflammatory response 49 . Accordingly, studies in the liver of Gal-3 knockout mice indicate attenuation of inflammation, hepatocyte injury and fibrosis, and insulin resistance 26 , 47 .…”

Galectin-3, Possible Role in Pathogenesis of Periodontal Diseases and Potential Therapeutic Target

“…Microglia secrete Gal-3 which binds TLR-4 expressed by neighboring microglia leading to their classical activation with enhanced production of pro-inflammatory cytokines ( Dumic et al, 2006 ). Gal-3 activates NLRP3 inflammasome, stimulating thus inflammatory phenotype of macrophages and is implicated in the pathogenesis of many chronic inflammatory diseases ( Pejnovic et al, 2013 ; Arsenijevic et al, 2016 ; Simovic Markovic et al, 2016 ; Tian et al, 2016 ; Arsenijevic et al, 2019 ; Liao et al, 2019 ; Arsenijevic et al, 2020 ). Having in mind that tissue-resident macrophages in gingiva play the role in the maintanance of mucosal immunity and healing ( Grainger et al, 2017 ) modulation of their activity by Gal-3 certainly contributes to immunopathogenesis of periodontal diseases.…”