Please use this identifier to cite or link to this item: https://scidar.kg.ac.rs/handle/123456789/9054
Title: Galectin-3 plays an important pro-inflammatory role in the induction phase of acute colitis by promoting activation of NLRP3 inflammasome and production of IL-1β in macrophages
Authors: Simovic Markovic, Bojana
Nikolić A.
Gazdic, Marina
Bojic, Sanja
Vucicevic, Ljubica
Kosic, Milica
Mitrovic M.
Milosavljevic, Milos
Besra, Gurdyal
Trajkovic V.
Arsenijevic, Nebojsa
Lukic, Miodrag
Volarevic, Vladislav
Journal: Journal of Crohn's and Colitis
Issue Date: 1-May-2016
Abstract: © 2016 European Crohn's and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. Background and Aims: Galectin-3 [Gal-3] is an endogenous lectin with a broad spectrum of immunoregulatory effects: It plays an important role in autoimmune/inflammatory and malignant diseases, but the precise role of Gal-3 in pathogenesis of ulcerative colitis is still unknown. Methods: We used a model of dextran sulphate sodium [DSS]-induced acute colitis. The role of Gal-3 in pathogenesis of this disease was tested by evaluating disease development in Gal-3 deficient mice and administration of Gal-3 inhibitor. Disease was monitored by clinical, histological, histochemical, and immunophenotypic investigations. Adoptive transfer was used to detect cellular events in pathogenesis. Results: Genetic deletion or pharmacological inhibition of Gal-3 significantly attenuate DSS-induced colitis. Gal-3 deletion suppresses production of pro-inflammatory cytokines in colonic macrophages and favours their alternative activation, as well as significantly reducing activation of NOD-like receptor family, pyrin domain containing 3 [NLRP3] inflammasome in macrophages. Peritoneal macrophages isolated from untreated Gal-3-/- mice and treated in vitro with bacterial lipopolysaccharide or DSS produce lower amounts of tumour necrosis factor alpha [TNF-α] and interleukin beta [IL-1β] when compared with wild type [WT] cells. Genetic deletion of Gal-3 did not directly affect total neutrophils, inflammatory dendritic cells [DCs] or natural killer [NK] T cells. However, the total number of CD11c+ CD80+ DCs which produce pro-inflammatory cytokines, as well as TNF-α and IL-1β producing CD45+ CD11c- Ly6G+ neutrophils were significantly lower in colons of Gal-3-/- DSS-treated mice. Adoptive transfer of WT macrophages significantly enhanced the severity of disease in Gal-3-/- mice. Conclusions: Gal-3 expression promotes acute DSS-induced colitis and plays an important pro-inflammatory role in the induction phase of colitis by promoting the activation of NLRP3 inflammasome and production of IL-1β in macrophages.
URI: https://scidar.kg.ac.rs/handle/123456789/9054
Type: Article
DOI: 10.1093/ecco-jcc/jjw013
ISSN: 18739946
SCOPUS: 84982223827
Appears in Collections:Faculty of Medical Sciences, Kragujevac
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