2. Academic Validation
  3. Death-associated protein kinase 1 mediates interleukin-1β production through regulating inlfammasome activation in Bv2 microglial cells and mice

Death-associated protein kinase 1 mediates interleukin-1β production through regulating inlfammasome activation in Bv2 microglial cells and mice

  • Sci Rep. 2018 Jul 2;8(1):9930. doi: 10.1038/s41598-018-27842-y.
Limin Song 1 2,  Lei Pei 3,  Lisha Hu 1 2,  Shangwen Pan 4 2,  Wei Xiong 4 2,  Min Liu 1 2,  Yan Wu 5,  You Shang 6 7,  Shanglong Yao 1 2
Affiliations

Affiliations

  • 1 Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 2 Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 3 Department of Neurobiology, Tongji Medical Collge, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 4 Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
  • 5 Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. wuyan_120@163.com.
  • 6 Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. you_shang@yahoo.com.
  • 7 Institute of Anesthesiology and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. you_shang@yahoo.com.
PMID: 29967321 DOI: 10.1038/s41598-018-27842-y
Abstract

Interleukin-1β (IL-1β) plays a crucial role in mediating inflammation and innate immunity response in the central nervous system. Death-associated protein kinase 1 (DAPK1) was shown to be involved in several cellular processes. Here, we investigated the effects of DAPK1 on IL-1β production in microglial cells. We used a combination of in vitro (Bv2 microglial cell cultures) and in vivo (mice injected with Amyloid-β (Aβ)) techniques to address the role of Caspase-1 activation in release of IL-1β. DAPK1 involvement was postulated through genetic approaches and pharmacological blockade of this Enzyme. We found that Aβ25-35 stimulation induced IL-1β production and Caspase-1 activation in LPS-primed Bv2 cells and mice. DAPK1 knockdown and catalytic activity inhibition reduced IL-1β maturation and Caspase-1 activation, nevertheless, DAPK1 overexpression attenuated these effects. Aβ25-35-induced lysosomal Cathepsin B leakage was required for DAPK1 activation. Furthermore, repeated DAPK1 inhibitor treatment ameliorated the memory impairment in Aβ25-35-injected mice. Taken together, our findings suggest that DAPK1 facilitates Aβ25-35-induced IL-1β production through regulating Caspase-1 activation in microglial cells.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15513
    98.26%, DAPK Inhibitor