Methylglyoxal treatment of MH-S cell line induces apoptosis and immune response

Mycobacteria-induced apoptosis of macrophages plays an important role in modulation of the host immune response involving TNF-alpha as major cytokine. The underlying mechanisms are still ill-defined. Here, we show for the first time that methylglyoxal (MG) and AGEs levels were elevated during mycobacterial infection of macrophages and that their increased levels mediated mycobacteria-induced apoptotic and immune response of macrophages. Moreover, we show that high levels of AGEs were formed at the sites of pulmonary tuberculosis. This observation represents the first evidence of the potential involvement of AGEs in tuberculosis and in infectious diseases in general. Global gene expression profiling of MG-treated macrophages reveals diversified potential roles of MG in cellular processes, including apoptosis, immune response, and growth regulation. The results of this study provide new insights into intervention strategies to develop therapeutic tools against infectious diseases in which MG and AGE production plays critical roles.

12

Rachman H, Kim N, Ulrichs T, Baumann S, Pradl L, Nasser Eddine A, Bild M, Rother M, Kuban RJ, Lee JS, Hurwitz R, Brinkmann V, Kosmiadi GA, Kaufmann SH