Glycolysis and the Pentose Phosphate Pathway Promote LPS-Induced NOX2 Oxidase- and IFN-β-Dependent Inflammation in Macrophages.

Autor:	Erlich JR; School of Health and Biomedical Sciences, RMIT University, Bundoora 3083, Australia., To EE; School of Health and Biomedical Sciences, RMIT University, Bundoora 3083, Australia.; F.M. Kirby Neurobiology Centre, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA., Luong R; Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton 3800, Australia., Liong F; School of Health and Biomedical Sciences, RMIT University, Bundoora 3083, Australia., Liong S; School of Health and Biomedical Sciences, RMIT University, Bundoora 3083, Australia., Oseghale O; School of Health and Biomedical Sciences, RMIT University, Bundoora 3083, Australia., Miles MA; School of Health and Biomedical Sciences, RMIT University, Bundoora 3083, Australia., Bozinovski S; School of Health and Biomedical Sciences, RMIT University, Bundoora 3083, Australia., Brooks RD; Clinical and Health Sciences, University of South Australia, Adelaide 5001, Australia., Vlahos R; School of Health and Biomedical Sciences, RMIT University, Bundoora 3083, Australia., Chan S; School of Health and Biomedical Sciences, RMIT University, Bundoora 3083, Australia., O'Leary JJ; Discipline of Histopathology, School of Medicine, Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, D08 XW7X Dublin, Ireland.; Sir Patrick Dun's Laboratory, Central Pathology Laboratory, St James's Hospital, D08 XW7X Dublin, Ireland.; Emer Casey Research Laboratory, Molecular Pathology Laboratory, The Coombe Women and Infants University Hospital, D08 XW7X Dublin, Ireland.; CERVIVA Research Consortium, Trinity College Dublin, D08 XW7X Dublin, Ireland., Brooks DA; Clinical and Health Sciences, University of South Australia, Adelaide 5001, Australia.; Discipline of Histopathology, School of Medicine, Trinity Translational Medicine Institute (TTMI), Trinity College Dublin, D08 XW7X Dublin, Ireland., Selemidis S; School of Health and Biomedical Sciences, RMIT University, Bundoora 3083, Australia.
Jazyk:	angličtina
Zdroj:	Antioxidants (Basel, Switzerland) [Antioxidants (Basel)] 2022 Jul 29; Vol. 11 (8). Date of Electronic Publication: 2022 Jul 29.
DOI:	10.3390/antiox11081488
Abstrakt:	Macrophages undergo a metabolic switch from oxidative phosphorylation to glycolysis when exposed to gram-negative bacterial lipopolysaccharide (LPS), which modulates antibacterial host defence mechanisms. Here, we show that LPS treatment of macrophages increased the classical oxidative burst response via the NADPH oxidase (NOX) 2 enzyme, which was blocked by 2-deoxyglucose (2-DG) inhibition of glycolysis. The inhibition of the pentose phosphate pathway with 6-aminonicotinamide (6-AN) also suppressed the LPS-induced increase in NOX2 activity and was associated with a significant reduction in the mRNA expression of NOX2 and its organizer protein p47phox. Notably, the LPS-dependent enhancement in NOX2 oxidase activity was independent of both succinate and mitochondrial reactive oxygen species (ROS) production. LPS also increased type I IFN-β expression, which was suppressed by 2-DG and 6-AN and, therefore, is dependent on glycolysis and the pentose phosphate pathway. The type I IFN-β response to LPS was also inhibited by apocynin pre-treatment, suggesting that NOX2-derived ROS promotes the TLR4-induced response to LPS. Moreover, recombinant IFN-β increased NOX2 oxidase-dependent ROS production, as well as NOX2 and p47phox expression. Our findings identify a previously undescribed molecular mechanism where both glycolysis and the pentose phosphate pathway are required to promote LPS-induced inflammation in macrophages.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu