The paradoxical role of the transient receptor potential vanilloid 1 receptor in inflammation

Alawi, Khadija M.; Keeble, Julie

doi:10.1016/j.pharmthera.2009.10.005

Cited by 151 publications

(117 citation statements)

References 208 publications

Supporting

Mentioning

113

Contrasting

Order By: Relevance

“…This dual modulatory effect of NADA has previously been proposed to finetune the transmission of glutamate onto dopamine neurons and explain such observations that NADA has both pro-and anti-nociceptive properties (39,41). Based on our observations that NADA may reduce inflammation through CB 1 R/CB 2 R, but promote inflammation through TRPV1, a logical conclusion is that NADA may also fine-tune the inflammatory activation of ECs (124). A model based on our observations with NADA in LPS-treated HMVEC-lung is shown in Fig.…”

Section: Discussionsupporting

confidence: 75%

The Endocannabinoid/Endovanilloid N-Arachidonoyl Dopamine (NADA) and Synthetic Cannabinoid WIN55,212-2 Abate the Inflammatory Activation of Human Endothelial Cells

Wilhelmsen

Khakpour

Tran

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:The endothelium is centrally involved in acute inflammatory disorders. Results: WIN55,212-2 and the endocannabinoid N-arachidonoyl dopamine (NADA), but not anandamide nor 2-arachidonoylglycerol, reduce endothelial activation by bacterial Toll-like receptor agonists and TNF␣. Conclusion: NADA is a newly identified endogenous regulator of endothelial inflammation. Significance: The endothelial endocannabinoid system represents a novel immune regulatory system that could be exploited therapeutically.

show abstract

Section: Discussionsupporting

confidence: 75%

The Endocannabinoid/Endovanilloid N-Arachidonoyl Dopamine (NADA) and Synthetic Cannabinoid WIN55,212-2 Abate the Inflammatory Activation of Human Endothelial Cells

Wilhelmsen

Khakpour

Tran

et al. 2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Although the mechanism of TRPV1 channel activation after irradiation is still unknown, possible mediators include radiation-induced reactive oxygen species and secondary generation of nitric oxide in irradiated cells, 33) or radiation-induced extracellular release of ATP from cells, we have reported. [34][35][36][37] On the other hand, it is well known that TRPV1 channel is involved in inflammation and pain sensation, [38][39][40][41] and TRPV1 channel inhibitors are candidates as analgesic drugs to relieve cancer pain. 42,43) Therefore, TRPV1 inhibitors might offer dual benefits in cancer therapy, having both anti-inflammatory and radiosensitizing actions.…”

Section: Resultsmentioning

confidence: 99%

Radiosensitizing Effect of TRPV1 Channel Inhibitors in Cancer Cells

Nishino

Tanamachi

Nakanishi

et al. 2016

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Radiosensitizers are used in cancer therapy to increase the γ-irradiation susceptibility of cancer cells, including radioresistant hypoxic cancer cells within solid tumors, so that radiotherapy can be applied at doses sufficiently low to minimize damage to adjacent normal tissues. Radiation-induced DNA damage is repaired by multiple repair systems, and therefore these systems are potential targets for radiosensitizers. We recently reported that the transient receptor potential vanilloid type 1 (TRPV1) channel is involved in early responses to DNA damage after γ-irradiation of human lung adenocarcinoma A549 cells. Therefore, we hypothesized that TRPV1 channel inhibitors would have a radiosensitizing effect by blocking repair of radiation-induced cell damage. Here, we show that pretreatment of A549 cells with the TRPV1 channel inhibitors capsazepine, AMG9810, SB366791 and BCTC suppressed the γ-ray-induced activation of early DNA damage responses, i.e., activation of the protein kinase ataxia-telangiectasia mutated (ATM) and accumulation of p53-binding protein 1 (53BP1). Further, the decrease of survival fraction at one week after γ-irradiation (2.0 Gy) was enhanced by pretreatment of cells with these inhibitors. On the other hand, inhibitor pretreatment did not affect cell viability, the number of apoptotic or necrotic cells, or DNA synthesis at 24 h after irradiation. These results suggest that inhibition of DNA repair by TRPV1 channel inhibitors in irradiated A549 cells caused gradual loss of proliferative ability, rather than acute facilitation of apoptosis or necrosis. TRPV1 channel inhibitors could be novel candidates for radiosensitizers to improve the efficacy of radiation therapy, either alone or in combination with other types of radiosensitizers. Key words γ-ray; radiosensitizer; transient receptor potential vanilloid type 1 channelRadiation therapy plays an important role in treatment of numerous cancers, 1) because ionizing radiation induces potentially lethal DNA damage, such as DNA double-strand breaks (DSBs). Although DSBs cause cell death or genomic instability, 2,3) they can be repaired by mechanisms such as non-homologous end joining (NHEJ) or homologous recombination (HR). NHEJ rejoins the DNA ends without requiring sequence homologies, and is mediated by a DNA-dependent protein kinase holoenzyme. On the other hand, HR processes use undamaged homologous DNA sequences (sister chromatid or the homologous chromosome) to ensure the fidelity of the repair process. [4][5][6] The DNA damage response pathways protect genomic integrity and act as a barrier against cancer, 7) and are important for recovery of irradiated normal cells. However, overexpression of DNA repair proteins is involved in radioresistance of cancer cells, [8][9][10] and therefore these mechanisms also decrease the efficiency of radiation therapy.Since ionizing radiation does not discriminate between cancer cells and normal cells, damage to normal tissues is usually a dose-limiting factor in radiation therapy. In addition, many solid ...

show abstract

“…For example, neuroendocrine hormones have well-known anti-inflammatory activities, first documented for corticosteroids in the arthritis context (2). Subsequently, motor neurons, the sympathetic nervous system (SNS), the parasympathetic nervous system (PNS), and sensory fibers have all been documented to modulate inflammation (3)(4)(5).…”

mentioning

confidence: 99%

Denervation protects limbs from inflammatory arthritis via an impact on the microvasculature

Stangenberg

Burzyn

Binstadt

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Significance Individuals who suffer paralysis on one side of the body and then develop rheumatoid arthritis show joint inflammation only on the neurologically intact side. We successfully modeled hemiplegia-induced protection from arthritis by transferring arthritogenic serum from K/BxN mice into recipients that had undergone unilateral sciatic and femoral nerve transection. Protection from serum-transferred arthritis could not be achieved by inhibiting the sympathetic, parasympathetic, or sensory arms of the nervous system. However, nerve transection did inhibit the joint-localized, inflammation-enhancing vascular leak rapidly induced by arthritogenic immune complexes and suggestively altered the transcriptome of the ankle microvasculature.

show abstract

The paradoxical role of the transient receptor potential vanilloid 1 receptor in inflammation

Cited by 151 publications

References 208 publications

The Endocannabinoid/Endovanilloid N-Arachidonoyl Dopamine (NADA) and Synthetic Cannabinoid WIN55,212-2 Abate the Inflammatory Activation of Human Endothelial Cells

The Endocannabinoid/Endovanilloid N-Arachidonoyl Dopamine (NADA) and Synthetic Cannabinoid WIN55,212-2 Abate the Inflammatory Activation of Human Endothelial Cells

Radiosensitizing Effect of TRPV1 Channel Inhibitors in Cancer Cells

Denervation protects limbs from inflammatory arthritis via an impact on the microvasculature

Contact Info

Product

Resources

About