Please use this identifier to cite or link to this item: https://www.um.edu.mt/library/oar/handle/123456789/96578
Title: Role of myeloid Tet methylcytosine dioxygenase 2 in pulmonary and peritoneal inflammation induced by lipopolysaccharide and peritonitis induced by Escherichia coli
Authors: Qin, Wanhai
Brands, Xanthe
Matsumoto, Hisatake
Butler, Joe M.
Veer, Cornelis Van't
Vos, Alex F. de
Roelofs, Joris J. T. H.
Scicluna, Brendon P.
Poll, Tom van der
Keywords: Escherichia coli -- Biotechnology
Infection
Inflammation -- Immunological aspects
Macrophages -- Research
Antibacterial agents
DNA-binding proteins
Inflammation -- Immunological aspects
Interleukins -- Receptors
Endotoxins -- Analysis
Issue Date: 2021
Publisher: MDPI AG
Citation: Qin, W., Brands, X., Matsumoto, H., Butler, J. M., van’t Veer, C., de Vos, A. F., ... & van der Poll, T. (2021). Role of Myeloid Tet Methylcytosine Dioxygenase 2 in Pulmonary and Peritoneal Inflammation Induced by Lipopolysaccharide and Peritonitis Induced by Escherichia coli. Cells, 11(1), 82.
Abstract: Tet methylcytosine dioxygenase 2 (Tet2) mediates demethylation of DNA. We here sought to determine the expression and function of Tet2 in macrophages upon exposure to lipopolysaccharide (LPS), and in the host response to LPS induced lung and peritoneal inflammation, and during Escherichia (E.) coli induced peritonitis. LPS induced Tet2 expression in mouse macrophages and human monocytes in vitro, as well as in human alveolar macrophages after bronchial instillation in vivo. Bone marrow-derived macrophages from myeloid Tet2 deficient (Tet2fl/flLysMCre) mice displayed enhanced production of IL-1β, IL-6 and CXCL1 upon stimulation with several Toll-like receptor agonists; similar results were obtained with LPS stimulated alveolar and peritoneal macrophages. Histone deacetylation was involved in the effect of Tet2 on IL-6 production, whilst methylation at the Il6 promoter was not altered by Tet2 deficiency. Tet2fl/flLysMCre mice showed higher IL-6 and TNF levels in bronchoalveolar and peritoneal lavage fluid after intranasal and intraperitoneal LPS administration, respectively, whilst other inflammatory responses were unaltered. E. coli induced stronger production of IL-1β and IL-6 by Tet2 deficient peritoneal macrophages but not in peritoneal lavage fluid of Tet2fl/flLysMCre mice after in vivo intraperitoneal infection. Tet2fl/flLysMCre mice displayed enhanced bacterial growth during E. coli peritonitis, which was associated with a reduced capacity of Tet2fl/flLysMCre peritoneal macrophages to inhibit the growth of E. coli in vitro. Collectively, these data suggest that Tet2 is involved in the regulation of macrophage functions triggered by LPS and during E. coli infection.
URI: https://www.um.edu.mt/library/oar/handle/123456789/96578
Appears in Collections:Scholarly Works - FacHScABS



Items in OAR@UM are protected by copyright, with all rights reserved, unless otherwise indicated.