Critical Role of Methylglyoxal and AGE in Mycobacteria-Induced Macrophage Apoptosis and Activation
Helmy Rachman,Nayoung Kim,Timo Ulrichs,Sven Baumann,Lydia Pradl,Ali Nasser Eddine,Matthias Bild,Marion Rother,Ralf-Jürgen Kuban,Jong Seok Lee,Robert Hurwitz,Volker Brinkmann,George A. Kosmiadi,Stefan H. E. Kaufmann +13 more
TLDR
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 macocytes are demonstrated, providing first evidence for the involvement of MG and AGE in TB.Abstract:
Apoptosis and activation of macrophages play an important role in the host response to mycobacterial infection involving TNF-a 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.read more
Citations
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