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CRID3 , a blocker of apoptosis associated speck like protein containing a card, ameliorates murine spinal cord injury by improving local immune microenvironment
Jian-Guo Hu
Bengbu Medical College
Corresponding Author
He-zuo Lü
the First Affiliated Hospital of Bengbu Medical College
Corresponding Author
ORCiD: https://orcid.org/0000-0002-3889-835X
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Journal of Neuroinflammation.
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. In this study, 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 also been found.
Conclusions: CRID3 may ameliorates 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
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CURRENT STATUS: Published
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Received 22 Jun, 2020
Reviewer #2 agreed
On 07 Jun, 2020
Reviewer #1 agreed
On 12 May, 2020
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This preprint is under consideration at Journal of Neuroinflammation. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
CRID3 , a blocker of apoptosis associated speck like protein containing a card, ameliorates murine spinal cord injury by improving local immune microenvironment
Jian-Guo Hu
Bengbu Medical College
Corresponding Author
He-zuo Lü
the First Affiliated Hospital of Bengbu Medical College
Corresponding Author
ORCiD: https://orcid.org/0000-0002-3889-835X
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 1
Posted 13 Apr, 2020
Published
On 29 Aug, 2020
No community comments so far
Review #2 received
Received 06 Jul, 2020
Editorial decision: Major Revision
On 06 Jul, 2020
Review #1 received
Received 22 Jun, 2020
Reviewer #2 agreed
On 07 Jun, 2020
Reviewer #1 agreed
On 12 May, 2020
Reviewers invited
Invitations sent on 20 Apr, 2020
Editor invited
On 09 Apr, 2020
Editor assigned
On 08 Apr, 2020
First submitted
On 07 Apr, 2020
Submission checks complete
On 07 Apr, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Neurobiology of Disease
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Journal of Neuroinflammation.
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. In this study, 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 also been found.
Conclusions: CRID3 may ameliorates 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.
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Figure 4
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Figure 10
Figure 11