TRPV4 Regulates Soman-Induced Status Epilepticus and Secondary Brain Injury via NMDA Receptor and NLRP3 Inflammasome

Wang, Shuai; He, Huanhuan; Long, Jianhai; Sui, Xin; Yang, Jun; Lin, Guo-Dong; Wang, Qian; Wang, Yongan; Luo, Yuan

doi:10.1007/s12264-021-00662-3

Cited by 28 publications

(15 citation statements)

References 43 publications

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“…These results suggest that TRPV4 activation promotes NFκB-NLRP3 activation and inflammation in response to pressure overload, which further demonstrates a mechanism for TRPV4 in this response. Several other studies have also found that TRPV4 activation induces inflammation through the NFκB-NLRP3 signaling pathway ( Wang et al, 2021 ; Wang et al, 2019b ). In addition, we found that GSK790A also induced rapid phosphorylation of NFκB, which could be prevented by KN-93 for CaMKII inhibition, and this implies that CaMKII is involved in TRPV4 activation-induced phosphorylation of NFκB.…”

Section: Discussionmentioning

confidence: 86%

Activation of transient receptor potential vanilloid 4 is involved in pressure overload-induced cardiac hypertrophy

Zou

Zhang

et al. 2022

eLife

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Previous studies, including our own, have demonstrated that transient receptor potential vanilloid 4 (TRPV4) is expressed in hearts and implicated in cardiac remodeling and dysfunction. However, the effects of TRPV4 on pressure overload-induced cardiac hypertrophy remain unclear. In this study, we found that TRPV4 expression was significantly increased in mouse hypertrophic hearts, human failing hearts, and neurohormone-induced hypertrophic cardiomyocytes. Deletion of TRPV4 attenuated transverse aortic constriction (TAC)-induced cardiac hypertrophy, cardiac dysfunction, fibrosis, inflammation, and the activation of NFκB - NOD - like receptor pyrin domain-containing protein 3 (NLRP3) in mice. Furthermore, the TRPV4 antagonist GSK2193874 (GSK3874) inhibited cardiac remodeling and dysfunction induced by TAC. In vitro, pretreatment with GSK3874 reduced the neurohormone-induced cardiomyocyte hypertrophy and intracellular Ca2+ concentration elevation. The specific TRPV4 agonist GSK1016790A (GSK790A) triggered Ca2+ influx and evoked the phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). But these effects were abolished by removing extracellular Ca2+ or GSK3874. More importantly, TAC or neurohormone stimulation-induced CaMKII phosphorylation was significantly blocked by TRPV4 inhibition. Finally, we show that CaMKII inhibition significantly prevented the phosphorylation of NFκB induced by GSK790A. Our results suggest that TRPV4 activation contributes to pressure overload-induced cardiac hypertrophy and dysfunction. This effect is associated with upregulated Ca2+/CaMKII mediated activation of NFκB-NLRP3. Thus, TRPV4 may represent a potential therapeutic drug target for cardiac hypertrophy and dysfunction after pressure overload.

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Section: Discussionmentioning

confidence: 86%

Activation of transient receptor potential vanilloid 4 is involved in pressure overload-induced cardiac hypertrophy

Zou

Zhang

et al. 2022

eLife

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“…NLRP3 inflammasome becomes a target for the prevention and treatment of central nervous system diseases. 41 , 42 The expression of NLRP3 inflammasome in BCP increased significantly in a time-dependent manner and was mainly co-localized with NeuN in SDH. 43 We found that BCP upregulated NLRP3, IL-1β, and caspase-1 expression in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 99%

CXCR1 participates in bone cancer pain induced by Walker 256 breast cancer cells in female rats

Zhao

et al. 2022

Mol Pain

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Bone cancer pain (BCP) is a clinically intractable mixed pain, involving inflammation and neuropathic pain, and its mechanisms remain unclear. CXC chemokine receptor 1 (CXCR1, IL-8RA) and 2 (CXCR2, IL-8RB) are high-affinity receptors for interleukin 8 (IL8). According to previous studies, CXCR2 plays a crucial role in BCP between astrocytes and neurons, while the role of CXCR1 remains unclear. The objective of this study was to investigate the role of CXCR1 in BCP. We found that CXCR1 expression increased in the spinal dorsal horn. Intrathecal injection of CXCR1 siRNA effectively attenuated mechanical allodynia and pain-related behaviors in rats. It was found that CXCR1 was predominantly co-localized with neurons. Intrathecal injection of CXCR1-siRNA reduced phosphorylated JAK2/STAT3 protein levels and the NLRP3 inflammasome (NLRP3, caspase1, and IL-1β) levels. Furthermore, in vitro cytological experiments confirmed this conclusion. The study results suggest that the spinal chemokine receptor CXCR1 activation mediates BCP through JAK2/STAT3 signaling pathway and NLRP3 inflammasome (NLRP3, caspase1, and IL-1β).

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“…The Abx-treated Casp1 KO group demonstrated no pain behavior attenuation and less expression of the inflammation-associated nociceptors CB2, PAR2 and TRPV4. These nociceptors have been shown to regulate the inflammasome pathway in a model of brain injury and demyelination, where the deletion or inhibition of TRPV4 reduced the activation of the NLRP3 inflammasome pathway [ 35 , 36 ]. In addition, administration of CB2 agonists or PAR-2 antagonist to mice with inflammatory pain or with knee joint pain led to the reduction of NLRP3 inflammasome activation [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Inflammasome Signaling Regulates the Microbial–Neuroimmune Axis and Visceral Pain in Mice

Aguilera

Rossini

Hickey

et al. 2021

IJMS

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Interactions between the intestinal microbiota, immune system and nervous system are essential for homeostasis in the gut. Inflammasomes contribute to innate immunity and brain–gut interactions, but their role in microbiota–neuro–immune interactions is not clear. Therefore, we investigated the effect of the inflammasome on visceral pain and local and systemic neuroimmune responses after antibiotic-induced changes to the microbiota. Wild-type (WT) and caspase-1/11 deficient (Casp1 KO) mice were orally treated for 2 weeks with an antibiotic cocktail (Abx, Bacitracin A and Neomycin), followed by quantification of representative fecal commensals (by qPCR), cecal short chain fatty acids (by HPLC), pathways implicated in the gut–neuro-immune axis (by RT-qPCR, immunofluorescence staining, and flow cytometry) in addition to capsaicin-induced visceral pain responses. Abx-treatment in WT-mice resulted in an increase in colonic macrophages, central neuro-immune interactions, colonic inflammasome and nociceptive receptor gene expression and a reduction in capsaicin-induced visceral pain. In contrast, these responses were attenuated in Abx-treated Casp1 KO mice. Collectively, the data indicate an important role for the inflammasome pathway in functional and inflammatory gastrointestinal conditions where pain and alterations in microbiota composition are prominent.

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TRPV4 Regulates Soman-Induced Status Epilepticus and Secondary Brain Injury via NMDA Receptor and NLRP3 Inflammasome

Cited by 28 publications

References 43 publications

Activation of transient receptor potential vanilloid 4 is involved in pressure overload-induced cardiac hypertrophy

Activation of transient receptor potential vanilloid 4 is involved in pressure overload-induced cardiac hypertrophy

CXCR1 participates in bone cancer pain induced by Walker 256 breast cancer cells in female rats

Inflammasome Signaling Regulates the Microbial–Neuroimmune Axis and Visceral Pain in Mice

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