| Summary: | 碩士 === 國立臺灣大學 === 動物學研究所 === 101 === Autophagy, a degradation system conserved from yeast to human, helps cells survive many stress conditions, such as starvation and pathogen infection. Under stress conditions, cells react and perform appropriate stress responses in order to increase the survival rates of cells or an individual. To best response to different stress conditions, there are many pathways reacting to different stresses. The mitogen-activated protein kinases (MAPK) cascade, which is activated after the stimulation of Toll-like receptors (TLR), responds to pathogen infection, and plays an important role in innate immunity. After MAPK activation, DUal Specificity Phosphatase 1 (DUSP1) is up-regulated, and it will down-regulate MAPK activities to decrease the immune responses. This negative feedback loop could maintain the activities of immune responses within a suitable level. Because autophagy is also correlated to the control of immune responses, it is of interests to know if DUSP1 affect autophagy activity. In this study, I found that DUSP1 regulated autophagy via controlling MAPKs activities. Inhibiting DUSP1 in raw 264.7 cells up regulated the activities of autophagy and two subsets of MAPKs (ERK and p38), and this activation of autophagy was not related to the change of the activity of mammalian target of rapamycin (mTOR) complex, which is the main regulator of starvation-induced autophagy. Furthermore, inhibiting ERK activity could block inhibiting DUSP1-induced autophagy. I also found that an autophagy inhibitor regulated IL-6 secretion and DUSP1 mRNA expression after TLR stimulation. Overall, these results suggest that DUSP1 and autophagy may mutually affect each other to maintain cellular physical homeostasis.
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