Activation of TAK1 by Chemotactic and Growth Factors, and Its Impact on Human Neutrophil Signaling and Functional Responses

摘要: The MAP3 kinase, TAK1, is known to act upstream of IKK and MAPK cascades in several cell types, typically activated response cytokines (e.g., TNF, IL-1) TLR ligands. In this article, we report that human neutrophils, TAK1 can also be by different classes inflammatory stimuli, namely, chemoattractants growth factors. After stimulation with such agents, becomes rapidly transiently activated. Blocking kinase activity a highly selective inhibitor (5z-7-oxozeaenol) attenuated the inducible phosphorylation ERK occurring these stimuli but had little or no effect on p38 PI3K. Inhibition impaired MEKK3 (but not MEKK1) activation fMLF. Moreover, both MEK/ERK module were found influence cytokine expression release fMLF- GM-CSF-activated whereas PI3K pathway influenced independently TAK1. Besides production, other responses under control neutrophils stimulated and/or GM-CSF, delayed apoptosis leukotriene biosynthesis. Our data further emphasize central role controlling signaling functional primary making it promising target for therapeutic intervention view foremost chronic conditions.