CRID3, a blocker of apoptosis associated speck like protein containing a card, ameliorates murine spinal cord injury by
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RESEARCH
Open Access
CRID3, a blocker of apoptosis associated speck like protein containing a card, ameliorates murine spinal cord injury by improving local immune microenvironment Yu-Qing Chen1,2,3,4†, Sai-Nan Wang1,2,3,4†, Yu-Jiao Shi1,2†, Jing Chen1,2,3,4, Shu-Qin Ding1, Jie Tang3,4, Lin Shen2, Rui Wang2, Hai Ding2, Jian-Guo Hu1,2* and He-Zuo Lü1,2,3,4*
Abstract Background: After spinal cord injury (SCI), destructive immune cell subsets are dominant in the local microenvironment, which are the important mechanism of injury. Studies have shown that inflammasomes play an important role in the inflammation following SCI, and apoptosis-associated speck-like protein containing a card (ASC) is the adaptor protein shared by inflammasomes. Therefore, we speculated that inhibiting ASC may improve the local microenvironment of injured spinal cord. Here, CRID3, a blocker of ASC oligomerization, was used to study its effect on the local microenvironment and the possible role in neuroprotection following SCI. Methods: Murine SCI model was created using an Infinite Horizon impactor at T9 vertebral level with a force of 50 kdynes and CRID3 (50 mg/kg) was intraperitoneally injected following injury. ASC and its downstream molecules in inflammasome signaling pathway were measured by western blot. The immune cell subsets were detected by immunohistofluorescence (IHF) and flow cytometry (FCM). The spinal cord fibrosis area, neuron survival, myelin preservation, and functional recovery were assessed. Results: Following SCI, CRID3 administration inhibited inflammasome-related ASC and caspase-1, IL-1β, and IL-18 activation, which consequently suppressed M1 microglia, Th1 and Th1Th17 differentiation, and increased M2 microglia and Th2 differentiation. Accordingly, the improved histology and behavior have also been found. Conclusions: CRID3 may ameliorate murine SCI by inhibiting inflammasome activation, reducing proinflammatory factor production, restoring immune cell subset balance, and improving local immune microenvironment, and early administration may be a promising therapeutic strategy for SCI. Keywords: Spinal cord injury, CRID3, Inflammasome, Apoptosis-associated speck-like protein containing a card, Immune microenvironment, Locomotor recovery
* Correspondence: [email protected]; [email protected] † Yu-Qing Chen, Sai-Nan Wang and Yu-Jiao Shi contributed equally to this work. 1 Clinical Laboratory, The First Affiliated Hospital of Bengbu Medical College, 233004 Bengbu, Anhui, People’s Republic of China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the ar
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