Activation of ERK1/2 and TNF-alpha production are mediated by calcium/calmodulin, and PKA signaling pathways during Mycobacterium bovis infection. The Journal of infection. [J Infect] Journal article | | Title | Activation of ERK1/2 and TNF-alpha production are mediated by calcium/calmodulin, and PKA signaling pathways during Mycobacterium bovis infection. | | Author(s) | Méndez-Samperio P, Trejo A, Miranda E | | Institution | Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, IPN, Carpio y Plan de Ayala, 11340 México, DF, México. pmendezs@bios.encb.ipn.mx | | Source | J Infect 2006 Feb; 52(2):147-53. | | Abstract | Mycobacterium bovis bacillus Calmette-Guérin (BCG)-induced tumor necrosis factor (TNF)-alpha secretion via an extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase-dependent mechanism is an important host defence mechanism against Mycobacterium tuberculosis in human monocytes. We now define distinct signaling pathways that regulate induction of TNF-alpha and activation of ERK1/2 by intracellular signaling mechanisms during M. bovis infection. We determined that M. bovis BCG-induced ERK 1/2 activation occurs through a mechanism that requires intracellular calcium and likely involves a calmodulin-sensitive step. In contrast, M. bovis BCG can induce p38 mapk activation by a calcium (Ca2+)/calmodulin-independent mechanism. Interestingly, we present evidence that M. bovis BCG activates protein kinase A (PKA), since pretreatment of monocytes with H-89, a inhibitor of PKA activity, blocked the ability of M. bovis BCG to induce ERK1/2 activation. These results were further supported by the fact that treatment of cells with KT5720, another well-described inhibitor of PKA activity, significantly diminished the effect of M. bovis BCG on ERK1/2 activation. Furthermore, secretion of TNF-alpha in M. bovis-infected human monocytes was also dependent on Ca2+/calmodulin, and PKA pathways. Finally, addition of H-89 significantly diminished TNF-alpha mRNA expression in M. bovis-infected human monocytes. These results indicate that the Ca2+/calmodulin, and PKA pathways play important regulatory roles in monocyte signaling upon M. bovis infection. | | Language | eng | | Pub Type(s) | Journal Article
| | PubMed ID | 16442440 |
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