Role of extracellular signal-regulated kinases 1 and 2 and p38 mitogen-activated protein kinase pathways in regulating replication of Penicillium marneffei in human macrophages.

摘要: Penicillium marneffei (P. marneffei) is a human pathogen which persists in macrophages and threatens the immunocompromised patients. To elucidate mechanisms involved, we investigated role of extracellular signal-regulated kinases 1 2 (ERK1/2) p38 mitogen-activated protein kinase (p38) pathways cytokine expression, phagosome-lysosome fusion replication P. marneffei-infected macrophages. Analysis both ERK1/2 showed rapid phosphorylation response to marneffei. Using specific inhibitors (SB203580) MAP kinase-1 (PD98059), found that were essential for marneffei-induced tumor necrosis factor-α production, whereas p38, but not ERK, was IL-10 production. Furthermore, presence PD98059 always decreased phagosomal acidification maturation increased intracellular multiplication marneffei, use SB203580 replication. These data suggest proper balance between may play an important controlling Our findings further indicate novel therapeutic avenue treating by stimulating or activating ERK1/2-dependent mechanisms.