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.
abstract: OBJECTIVE
  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.
authors.affiliation: Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Bojana
authors.initials: B
authors.lastname: Simovic Markovic
authors.affiliation: Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Nikolic
authors.affiliation: Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Marina
authors.initials: M
authors.lastname: Gazdic
authors.affiliation: Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Sanja
authors.initials: S
authors.lastname: Bojic
authors.affiliation: Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Ljubica
authors.initials: L
authors.lastname: Vucicevic
authors.affiliation: Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Milica
authors.initials: M
authors.lastname: Kosic
authors.affiliation: Department of Pathology, Faculty of Medical Sciences, Clinical Center Kragujevac, Kragujevac, Serbia.
authors.forename: Slobodanka
authors.initials: S
authors.lastname: Mitrovic
authors.affiliation: Department of Pathology, Faculty of Medical Sciences, Clinical Center Kragujevac, Kragujevac, Serbia.
authors.forename: Milos
authors.initials: M
authors.lastname: Milosavljevic
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham, UK.
authors.forename: Gurdyal
authors.initials: G
authors.lastname: Besra
authors.affiliation: Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Trajkovic
authors.affiliation: Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Nebojsa
authors.initials: N
authors.lastname: Arsenijevic
authors.affiliation: Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia miodrag.lukic@medf.kg.ac.rs.
authors.forename: Miodrag L
authors.initials: ML
authors.lastname: Lukic
authors.affiliation: Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Vladislav
authors.initials: V
authors.lastname: Volarevic
mesh_terms: D000208:Acute Disease; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000276:immunology / Q000378:metabolism; D003106:Colon / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D005434:Flow Cytometry; D037502:Galectin 3 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D016207:Cytokines; D037502:Galectin 3; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D016264:Dextran Sulfate
keywords: DSS colitis; Gal-3; NLRP3