Activation of ERK1/2 and TNF-alpha production are regulated by calcium/calmodulin signaling pathway during Penicillium marneffei infection within humand macrophages

摘要

Previous study have shown that Penicillium marneffei (P. marneffei)-induced TNF-alpha production via an extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase-dependent mechanism is an important host defence mechanism against P. marneffei in human macrophages. Therefore, we explore signaling pathway that regulates TNF-alpha secretion and activation of ERK1/2 by intracellular signaling mechanisms during P. marneffei infection. We found that ERK1/2 activation was dependent on the calcium/calmodulin/calmodulin kinase II pathway in P. marneffei-infected human macrophages. In contrast, P. marneffei-induced p38 MAPK activation was negatively regulated by calcium/calmodulin/calmodulin kinase II signaling pathway. Furthermore, TNF-alpha production in P. marneffei-infected human macrophages was also dependent on Ca2+/calmodulin/calmodulin kinase II pathway. These data suggest that Ca2+/calmodulin/calmodulin kinase II pathway plays vital regulatory roles in macrophage activation and subsequent cytokine production during P. marneffei infection. (C) 2016 Elsevier Ltd. All rights reserved.