Transient Receptor Potential Vanilloid 1 Modulates Central Inflammation in Multiple Sclerosis

Abstract

Introduction: Disease course of multiple sclerosis (MS) is negatively influenced by proinflammatory molecules released by activated T and B lymphocytes and local immune cells. The endovanilloid system plays different physiological functions, and preclinical data suggest that transient receptor potential vanilloid type 1 (TRPV1) could modulate neuroinflammation in this disorder.Methods: The effect of TRPV1 activation on the release of two main proinflammatory cytokines, tumor necrosis factor (TNF) and interleukin (IL)-6, was explored in activated microglial cells. Furthermore, in a group of 132 MS patients, the association between the cerebrospinal fluid (CSF) levels of TNF and IL-6 and a single nucleotide polymorphisms (SNP) influencing TRPV1 protein expression and function (rs222747) was assessed.Results: In in vitro experiments, TRPV1 stimulation by capsaicin significantly reduced TNF and IL-6 release by activated microglial cells. Moreover, the anti-inflammatory effect of TRPV1 activation was confirmed by another TRPV1 agonist, the resiniferatoxin (RTX), whose effects were significantly inhibited by the TRPV1 antagonist, 5-iodoresiniferatoxin (5-IRTX). Vice versa, BV2 pre-treatment with 5-IRTX increased the inflammatory response induced by LPS. Moreover, in MS patients, a significant association emerged between TRPV1 SNP rs222747 and CSF TNF levels. In particular, the presence of a G allele, known to result in increased TRPV1 protein expression and function, was associated to lower CSF levels of TNF.Conclusions: Our results indicate that TRPV1 influences central inflammation in MS by regulating cytokine release by activated microglial cells. The modulation of the endovanilloid system may represent a useful approach to contrast neuroinflammation in MS.

Palmitoylethanolamide (PEA) as a Potential Therapeutic Agent in Alzheimer’s Disease

“…In fact, TRPV1 channel activation has been linked to either anti-neuroinflammatory or pro-neuroinflammatory signaling (Kong et al, 2017). Interestingly, it has been recently reported that TRPV1 activation reduces central inflammation in multiple sclerosis (Stampanoni Bassi et al, 2019). Accordingly, neuroprotective effects of TRPV1 activation in animal models of Parkinson’s and Alzheimer’s diseases have been reported (Jiang et al, 2013; Nam et al, 2015; Jayant et al, 2016; Xu et al, 2017; Zhao et al, 2017; Balleza-Tapia et al, 2018).…”

The Endocannabinoid/Endovanilloid System in Bone: From Osteoporosis to Osteosarcoma

“…These cell features were inhibited once treated with a CB2 agonist [100]. TRPV1 reduces the release of pro-inflammatory cytokines, such as TNF and IL-6, when stimulated with specific agonists (i.e., capsaicin and RTX) [101]. Hence, considering the influence of the EC/EV system on inflammation and the connection between inflammation and tumor, it is worth investigating the therapeutic potential of the EC/EV system in tumor.…”

Shaoyao-Gancao Decoction Relieves Visceral Hyperalgesia in TNBS-Induced Postinflammatory Irritable Bowel Syndrome via Inactivating Transient Receptor Potential Vanilloid Type 1 and Reducing Serotonin Synthesis

“…Our results demonstrated that SGD could reverse the increase in TRPV1 expression. Chronic, low-grade inflammation has been implicated in disease progression and it is involved in the presence of IBS-like symptoms [ 32 ]. The plasma levels of proinflammatory cytokines, such as IL-6 and IL-8, were significantly elevated in IBS patients, and these inflammatory factors acted as the agonists of TRPV1 [ 32 ].…”

“…Chronic, low-grade inflammation has been implicated in disease progression and it is involved in the presence of IBS-like symptoms [ 32 ]. The plasma levels of proinflammatory cytokines, such as IL-6 and IL-8, were significantly elevated in IBS patients, and these inflammatory factors acted as the agonists of TRPV1 [ 32 ]. It has been reported that SGD possesses a multitude of pharmacological activities, including analgesic and anti-inflammatory properties.…”