Inhibition of cathepsin L alleviates the microglia-mediated neuroinflammatory responses through caspase-8 and NF-κB pathways

Publication date: Available online 6 October 2017
Source:Neurobiology of Aging
Author(s): Shaoqing Xu, Hui Zhang, Xiaodong Yang, Yiwei Qian, Qin Xiao
Cathepsin L (CTSL) has been shown to participate in the microglia-mediated neuroinflammation. However, role of CTSL in neuroinflammation remains to be elucidated. In this study, CTSL was found to be up-regulated upon lipopolysaccharide (LPS) stimulation. The neuroinflammatory responses upon LPS stimulation were ameliorated by inhibition or deficiency of CTSL in vitro or vivo. Treatment with conditioned medium of activated BV2 cells in SH-SY5Y cells showed that CTSL inhibition reduced microglia-mediated neurotoxicity. Further analysis indicated that CTSL was involved in the activation of caspase-8 and NF-κB, and overexpression of CTSL enhanced expression of inflammatory mediators in response to LPS via caspase-8 and NF-κB pathways. Moreover, mRNA level of CTSL in peripheral blood mononuclear cells from patients with Parkinson's disease (PD) was higher compared with controls. Level of CTSL was positively correlated with expression of inflammatory mediators and NF-κB in PD patients. Taken together, these findings suggested that inhibition of CTSL alleviated the neuroinflammatory responses through caspase-8 and NF-κB pathways, and blocking CTSL might provide some clues to control the excessive neuroinflammation.



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