Inhibition of NLRP3 inflammasome attenuates spinal cord injury‐induced lung injury in mice

Abstract

Spinal cord injury (SCI) is one kind of severe traumatic injury, resulting in systemic inflammatory response syndrome and secondary lung injury, which is an important pathological basis of respiratory complications. The nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome is an important cytosolic protein complex in many inflammatory diseases. Hence, it is inescapable to explore the effect of inhibition of NLRP3 inflammasome by inhibitors in a mouse SCI model, which was conducted by using the method of 30-G closing force aneurysm clipping at T6-T7 spinal segment for 1 min, followed by assessment of edema, histology, alveolar type II cell apoptosis, mitochondrial dysfunction, and neutrophil infiltration. In brief, our results showed that, NLRP3 inflammasome inhibitor BAY 11-7082 or A438079 inhibited activation of NLRP3 inflammasome, alleviated mitochondrial dysfunction, the number of macrophage and neutrophil, thereby attenuating alveolar type II cell apoptosis, lung edema, and histological injury. Taken together, our data reveal that NLRP3 inflammasome inhibitor BAY 11-7082 or A438079 attenuates the inflammatory response, reverses mitochondrial dysfunction, and subsequently alleviates secondary lung injury following SCI.

Clinic serum levels of Plin5 is therapeutic target of spinal cord injury and Plin5 reduced inflammation in spinal cord injury via silent information regulator 1 dependent inhibition of NLRP3 inflammasome

“…TLR can induce the activation of NF-κB, and is involved in the regulation of NLRP3 transcription by combining with the NF-κB-related sites in the NLRRP3 promoter (Mohammed et al, 2020). Relevant studies have also confirmed that NF-κB signaling pathway can regulate the protein expression of NLRP inflammasome, IL-18 precursor and IL-1β precursor in peripheral immune cells (Jiang et al, 2019;Zhang et al, 2020b;Su et al, 2020). The study investigated…”

“…NLRP3 is a member of the NLRs family and is the core component of the inflammasome (Pu et al, 2019). It contains three domains and its C-terminus is a leucine-rich repeat domain, whose main function is to identify danger-associated molecular patterns or pathogen-associated molecular patterns, also playing an important role in self-regulation and proteinprotein interaction (Jiang et al, 2019). TLR can induce the activation of NF-κB, and is involved in the regulation of NLRP3 transcription by combining with the NF-κB-related sites in the NLRRP3 promoter (Mohammed et al, 2020).…”

TI: NLRP3 Inflammasome-Dependent Pyroptosis in CNS Trauma: A Potential Therapeutic Target

“…Moreover, BAY 11-7082 inhibited microglia/macrophage activation and neutrophil infiltration, reduced glial proliferation and improved mitochondrial dysfunction, thereby reducing neuronal death and promoting motor recovery in SCI mice (Jiang W. et al, 2017). Notably, BAY 11-7082 contributed to improving secondary lung injury after SCI (Jiang et al, 2019). Additionally, in rats subjected to the CCI injury, Zheng et al showed that the synergistic effect of the coadministration of Bay-11-7082 and dexmedetomidine improved neuronal activity and inhibited microglial activation, as well as hippocampus tissues inflammation (Zheng B. et al, 2018).…”

Protective effects of melatonin on the white matter damage of neonatal rats by regulating NLRP3 inflammasome activity

“…Currently, a variety of inflammasomes have been identified, among which the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome can recognize various pathogens and pathogenic molecules; it is the most studied inflammasome. Previous studies have confirmed that NLRP3 inflammasomes are activated in a variety of diseases and are associated with subsequent inflammatory responses [3–5]. Additionally, NLRP3 inflammasomes have been found to be involved in poststroke brain injury [6,7].…”