Prohibitin plays a role in the functional plasticity of macrophages. (April 2022)

• Record Type: Journal Article
• Authors: Xu, Yang Xin Zi; Ande, Sudharsana Rao; Ikeogu, Nnamdi M.; Zhou, Kecheng; Uzonna, Jude E.; Mishra, Suresh
• Is Part Of: Molecular immunology. Volume 144(2022)
• Page Start: 152
• Page End: 165
• Publication Date: 2022-04
• Subjects: LPS lipopolysaccharide -- IL interleukin -- STAT signal transducer and activator of transcription -- ERK extracellular stress-regulated kinase -- OCR oxygen consumption rate -- PHB prohibitin -- IFNγ interferon γ -- TNFα tumor necrosis factor α -- sh short hairpin -- p phosphorylated -- HRP horse radish peroxidase -- SEM standard error of the mean; IL-4 -- LPS -- Prohibitin -- Macrophages -- Immunometabolism; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2022.02.014
• Languages: English
• ISSNs: 0161-5890

Abstract

Abstract: Immunometabolism plays a crucial role in the activation and functional plasticity of immune cells, which in large determines a variety of health and disease states. Factors that integrate immunometabolism in immune cell signaling and functions are beginning to be identified. Previously, we have reported that two transgenic mouse models, Mito-Ob and mutant Mito-Ob (m-Mito-Ob), overexpressing a pleiotropic protein, prohibitin (PHB) or a mutant form of PHB (Tyr114Phe-PHB or m-PHB), respectively, developed distinct immunometabolic phenotypes. Specifically, the immune phenotype appears to be driven by the monocytic cell lineage. Based on immunophenotyping of their splenocytes, we focused our attention on macrophages and hypothesized that PHB may play a role in regulating the two functionally polarized states, M1 and M2. Here, we report that macrophage polarization to the M1 and M2 phenotypes did not alter PHB protein level, but overexpression of PHB in macrophages differentially affected cytokine production in the two polarized states. Furthermore, we found that mutation of the Tyr 114 phosphorylation site in PHB affects ERK and STAT6 signaling, arginase synthesis and activity, and mitochondrial respiration in macrophages indicating an important role of PHB in integrating cell signaling events with cell metabolism. In summary, we have discovered that PHB is a crucial regulator in the functional plasticity of macrophages. These initial studies expect to lay the foundation for future research into the relationship between cell signaling events pertaining to immunometabolism in immune cell functions, which are integral components of immune-related health and disease. Highlights: Prohibitin integrates cell signaling with cell metabolism in macrophages. The role of prohibitin in macrophage biology involved Tyr114 phosphorylation site. Prohibitin pays a role in immunometabolism.