Methylglyoxal induced activation of murine peritoneal macrophages and surface markers of T lymphocytes in Sarcoma-180 bearing mice: involvement of MAP kinase, NF-κβ signal transduction pathway

Abstract

Methylglyoxal profoundly stimulates host's immune response against tumor cell by producing reactive oxygen intermediates (ROI's) and reactive nitrogen intermediates (RNI's) [Bhattacharyya, N., Pal, A., Patra, S., Haldar, A.K., Roy, S., Ray, M., 2008. Activation of macrophages and lymphocytes by methylglyoxal against tumor cells in the host. Int. Immunophar. 8 (11), 1503-1512]. Present study indicated that methylglyoxal stimulates iNOS activation by p38 MAPK-NF-κβ dependent pathway and ROS production by ERK and JNK activation in sarcoma-180 tumor bearing mice. Proinflammatory cytokines, for macrophage activation, IL-6 and IL-1β were also increased. Production of TLR 4 and TLR 9, which acts through the same signaling pathway, were also upregulated. Hence, concluded that methylglyoxal augmented the IL-6 and IL-1β, expression of TLR 4 and TLR 9 and produced MAPKs, important regulators of ROIs and RNIs. Methylglyoxal treatment also increased M-CSF, an upregulator of macrophage production. CD8 and CD4 molecules, associated with T_C and T_H cells respectively, were also increased. Overall methylglyoxal treatment is important for enhancement of macrophages and lymphocyte activation or immunomodulation against sarcoma-180 tumor.