title: Critical role of methylglyoxal and AGE in mycobacteria-induced macrophage apoptosis and activation.
abstract: Apoptosis and activation of macrophages play an important role in the host response to mycobacterial infection involving TNF-alpha as a critical autocrine mediator. The underlying mechanisms are still ill-defined. Here, we demonstrate elevated levels of methylglyoxal (MG), a small and reactive molecule that is usually a physiological product of various metabolic pathways, and advanced glycation end products (AGE) during mycobacterial infection of macrophages, leading to apoptosis and activation of macrophages. Moreover, we demonstrate abundant AGE in pulmonary lesions of tuberculosis (TB) patients. Global gene expression profiling of MG-treated macrophages revealed a diverse spectrum of functions induced by MG, including apoptosis and immune response. Our results not only provide first evidence for the involvement of MG and AGE in TB, but also form a basis for novel intervention strategies against infectious diseases in which MG and AGE play critical roles.
authors.affiliation: Max Planck Institute for Infection Biology, Department of Immunology, Berlin, Germany.
authors.forename: Helmy
authors.initials: H
authors.lastname: Rachman
authors.forename: Nayoung
authors.initials: N
authors.lastname: Kim
authors.forename: Timo
authors.initials: T
authors.lastname: Ulrichs
authors.forename: Sven
authors.initials: S
authors.lastname: Baumann
authors.forename: Lydia
authors.initials: L
authors.lastname: Pradl
authors.forename: Ali
authors.initials: A
authors.lastname: Nasser Eddine
authors.forename: Matthias
authors.initials: M
authors.lastname: Bild
authors.forename: Marion
authors.initials: M
authors.lastname: Rother
authors.forename: Ralf-Jürgen
authors.initials: RJ
authors.lastname: Kuban
authors.forename: Jong Seok
authors.initials: JS
authors.lastname: Lee
authors.forename: Robert
authors.initials: R
authors.lastname: Hurwitz
authors.forename: Volker
authors.initials: V
authors.lastname: Brinkmann
authors.forename: George A
authors.initials: GA
authors.lastname: Kosmiadi
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D054357:Chemokine CXCL10 / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D008262:Macrophage Activation / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D009161:Mycobacterium / Q000472:pathogenicity*; D009164:Mycobacterium Infections / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009163:Mycobacterium bovis / Q000472:pathogenicity; D011765:Pyruvaldehyde / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; D017127:Glycation End Products, Advanced; D014409:Tumor Necrosis Factor-alpha; D011765:Pyruvaldehyde