Activation and Regulation of NLRP3 Inflammasome by Intrathecal Application of SDF-1a in a Spinal Cord Injury Model
| Autor: | Mohammad Taghi Joghataei, Sonja Johann, Soraya Mehrabi, Adib Zendedel, Markus Kipp, Gholamreza Hassanzadeh, Cordian Beyer |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Male Time Factors Inflammasomes medicine.medical_treatment Neuroscience (miscellaneous) Cell Count Neuroprotection 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Glial Fibrillary Acidic Protein NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Gliosis RNA Messenger Rats Wistar Spinal cord injury Cellular localization Injections Spinal Spinal Cord Injuries Neurons Microglia business.industry Inflammasome medicine.disease Chemokine CXCL12 Cell biology CARD Signaling Adaptor Proteins Disease Models Animal 030104 developmental biology medicine.anatomical_structure Cytokine Neurology Tumor necrosis factor alpha business Neuroscience Inflammasome complex 030217 neurology & neurosurgery Locomotion medicine.drug |
| Zdroj: | Molecular neurobiology. 53(5) |
| ISSN: | 1559-1182 |
| Popis: | Stromal cell-derived factor-1 alpha (SDF-1a) or CXCL12 is an important cytokine with multiple functions in the brain during development and in adulthood. The inflammatory response initiated by spinal cord injury (SCI) involves the processing of interleukin-1beta (IL-1s) and IL-18 mediated by caspase-1 which is under the control of an intracellular multiprotein complex termed inflammasome. Using an SCI rat model, we found improved functional long-term recovery which is paralleled by a reduction of apoptosis after intrathecal treatment with SDF-1a. An intriguing aspect is that SDF-1a changed the number of neuroinflammatory cells in the damaged area. We further examined the cellular localization and sequential expression of several inflammasomes during SCI at 6 h, 24 h, 3 days, and 7 days as well as the role of SDF-1a as a regulatory factor for inflammasomes. Using 14-week old male Wistar rats, spinal cord contusion was applied at the thoracic segment 9, and animals were subsequently treated with SDF-1a via intrathecal application through an osmotic pump. SCI temporally increased the expression of the inflammasomes NLRP3, ASC, the inflammatory marker tumor necrosis factor-a (TNF-a), interleukin-1s (IL-1β) and IL-18. SDF-1a significantly reduced the levels of IL-18, IL-1b, TNF-a, NLRP3, ASC, and caspase-1. Immunofluorescence double-labeling demonstrated that microglia and neurons are major sources of the ASC and NLRP3 respectivley. Our data provide clear evidence that SCI stimulates a complex scenario of inflammasome activation at the injured site and that SDF-1a-mediated neuroprotection presumably depends on the attenuation of the inflammasome complex. |
| Databáze: | OpenAIRE |
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