The expressions of NLRP1, NLRP3, and AIM2 inflammasome complexes in the contusive spinal cord injury rat model and their responses to hormonal therapy

Majidpoor, J. and Khezri, Z. and Rostamzadeh, P. and Mortezaee, K. and Rezaie, M.J. and Fathi, F. and Abouzaripour, M. and Bariki, M.G. and Moradi, F. and Shirazi, R. and Joghataei, M.T. (2020) The expressions of NLRP1, NLRP3, and AIM2 inflammasome complexes in the contusive spinal cord injury rat model and their responses to hormonal therapy. Cell and Tissue Research, 381 (3). pp. 397-410.

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Spinal cord injury (SCI) is a devastating condition with a growing incidence in developing countries. The activity of inflammasome complexes initiates neuroinflammation, which is a key player in SCI pathogenesis. Here, NLRP1, NLRP3, and absent in melanoma 2 (AIM2) inflammasome complexes were assessed in the contusive (T6) SCI rats for their expression profiles and their response to hormonal therapy (10 mg/kg melatonin or 25 μg/kg 17β-estradiol E2 every 12 h until 72 h). Two phases was considered in this study: the dominant time of inflammasome activation, which was 72 h post-SCI and the response from each complex to hormonal therapy at this time. Gene and protein expressions of NLRP1, NLRP3, AIM2, ASC, and caspase-1 were evaluated by real-time PCR (for gene analysis), western blot, and immunohistochemistry (IHC), and biochemical presence of IL-18 and IL-1β in spinal cord tissue homogenates was analyzed by enzyme-linked immunosorbent assay (ELISA). The whole inflammasome complexes showed high expressions in the SCI group, while after hormonal therapy, these alterations were counteracted, which were more conspicuous for the NLRP1 and NLRP3. Melatonin had no predilection over E2 for such effect. Finally, the expression profile of signaling related to the synthesis (TLR4/NF-κB) and activation (NADPH oxidase 2 NOX2/TXNIP) of inflammasome complexes was surveyed, and there were low activities for the two pathways in SCI rats that underwent hormone therapy. From the findings, it is concluded that both melatonin and E2 are efficient to target inflammasome activation in the SCI rats. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

Item Type: Article
Additional Information: cited By 1
Uncontrolled Keywords: absent in melanoma 2; binding protein; cryopyrin; estradiol; immunoglobulin enhancer binding protein; inflammasome; interleukin 18; interleukin 1beta; interleukin 1beta converting enzyme; melatonin; nucleotide binding domain leucine rich repeat protein 1; protein ASC; reduced nicotinamide adenine dinucleotide phosphate oxidase 2; toll like receptor 4; unclassified drug, animal experiment; animal model; animal tissue; Article; controlled study; enzyme linked immunosorbent assay; gene expression profiling; hormonal therapy; immunohistochemistry; infant; male; nonhuman; pathogenesis; priority journal; protein expression; rat; real time polymerase chain reaction; spinal cord injury; tissue homogenate; treatment response; Western blotting
Subjects: WL Nervous System
QV Pharmacology
Depositing User: eprints admin
Date Deposited: 12 Jun 2021 04:49
Last Modified: 12 Jun 2021 04:49

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