title: Is monocyte- and macrophage-derived tissue transglutaminase involved in inflammatory processes?
abstract: Monocytes and macrophages are key players in inflammatory processes following an infection or tissue damage. Monocytes adhere and extravasate into the inflamed tissue, differentiate into macrophages, and produce inflammatory mediators to combat the pathogens. In addition, they take up dead cells and debris and, therefore, take part in the resolution of inflammation. The multifunctional enzyme tissue Transglutaminase (TG2, tTG) is known to participate in most of those monocyte- and macrophage-mediated processes. Moreover, TG2 expression and activity can be regulated by inflammatory mediators. In the present review, we selectively elaborate on the expression, regulation, and contribution of TG2 derived from monocytes and macrophages to inflammatory processes mediated by those cells. In addition, we discuss the role of TG2 in certain pathological conditions, in which inflammation and monocytes and/or macrophages are prominently present, including atherosclerosis, sepsis, and multiple sclerosis. Based on the studies and considerations reported in this review, we conclude that monocyte- and macrophage-derived TG2 is clearly involved in various processes contributing to inflammation. However, TG2's potential as a therapeutic target to counteract the possible detrimental effects or stimulate the potential beneficial effects on monocyte and macrophage responses during inflammation should be carefully considered. Alternatively, as TG2-related parameters can be used as a marker of disease, e.g., in celiac disease, or of disease-stage, e.g., in cancer, we put forward that this could be subject of research for monocyte- or macrophage-derived TG2 in inflammatory diseases.
authors.affiliation: Amsterdam Neuroscience, Department of Anatomy and Neurosciences, VU University Medical Center, De Boelelaan 1118, 1081 HV, Amsterdam, The Netherlands.
authors.forename: Navina L
authors.initials: NL
authors.lastname: Chrobok
authors.affiliation: Amsterdam Neuroscience, Department of Anatomy and Neurosciences, VU University Medical Center, De Boelelaan 1118, 1081 HV, Amsterdam, The Netherlands.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sestito
authors.affiliation: Amsterdam Neuroscience, Department of Anatomy and Neurosciences, VU University Medical Center, De Boelelaan 1118, 1081 HV, Amsterdam, The Netherlands.
authors.forename: Micha M M
authors.initials: MM
authors.lastname: Wilhelmus
authors.affiliation: Amsterdam Neuroscience, Department of Anatomy and Neurosciences, VU University Medical Center, De Boelelaan 1118, 1081 HV, Amsterdam, The Netherlands.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Drukarch
authors.affiliation: Amsterdam Neuroscience, Department of Anatomy and Neurosciences, VU University Medical Center, De Boelelaan 1118, 1081 HV, Amsterdam, The Netherlands. amw.vandam@vumc.nl.
authors.forename: Anne-Marie
authors.identifier: 0000-0003-4191-3941
authors.initials: AM
authors.lastname: van Dam
mesh_terms: D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000276:immunology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000276:immunology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D009000:Monocytes / Q000276:immunology* / Q000473:pathology; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D010587:Phagocytosis; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D018805:Sepsis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology; D011503:Transglutaminases / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; D051193:Toll-Like Receptors; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: Adhesion; Differentiation; Efferocytosis; Inflammation; Multiple sclerosis