Immunomodulatory and anti-oxidative effect of the direct TRPV1 receptor agonist capsaicin on Schwann cells

Thomas Grüter,Björn Ambrosius,Jeremias Motte,Kalliopi Pitarokoili,Rafael Klimas,Ralf Gold,Hussein Bachir,Alina Blusch,Melissa Sgodzai,Gisa Ellrichmann

doi:10.1186/s12974-020-01821-5

Thomas Grüter, Björn Ambrosius + Show 8 more

Open Access

https://doi.org/10.1186/s12974-020-01821-5

Copy DOI

Abstract

BackgroundOnly few studies describe the impact of nutritive factors on chronic inflammatory demyelinating polyneuropathy (CIDP), an inflammatory disease of the peripheral nervous system. The active component of chili pepper, capsaicin, is the direct agonist of the transient receptor potential channel vanilloid subfamily member 1. Its anti-inflammatory effect in the animal model experimental autoimmune neuritis (EAN) has been previously demonstrated.MethodsIn the present study, we describe the anti-inflammatory and anti-oxidative influence of capsaicin on Schwann cells (SCs) in an in vitro setting. Hereby, we analyze the effect of capsaicin on Schwann cells’ gene expression pattern, major histocompatibility complex class II (MHC-II) presentation, and H2O2-induced oxidative stress. Furthermore, the effect of capsaicin on myelination was examined in a SC-dorsal root ganglia (DRG) coculture by myelin basic protein staining. Finally, in order to investigate the isolated effect of capsaicin on SCs in EAN pathology, we transplant naïve and capsaicin pre-treated SCs intrathecally in EAN immunized rats and analyzed clinical presentation, electrophysiological parameters, and cytokine expression in the sciatic nerve.ResultsIn SC monoculture, incubation with capsaicin significantly reduces interferon gamma-induced MHC-II production as well as toll-like receptor 4 and intercellular adhesion molecule 1 mRNA expression. Calcitonin gene-related peptide mRNA production is significantly upregulated after capsaicin treatment. Capsaicin reduces H2O2-induced oxidative stress in SC in a preventive, but not therapeutic setting. In a SC-DRG coculture, capsaicin does not affect myelination rate. After intrathecal transplantation of naïve and capsaicin pre-treated SCs in EAN-immunized rats, naïve, but not capsaicin pre-treated intrathecal SCs, ameliorated EAN pathology in rats.ConclusionsIn conclusion, we were able to demonstrate a direct immunomodulatory and anti-oxidative effect of capsaicin in a SC culture by reduced antigen presentation and expression of an anti-inflammatory profile. Furthermore, capsaicin increases the resistance of SCs against oxidative stress. A primary effect of capsaicin on myelination was not proven. These results are in concordance with previous data showing an anti-inflammatory effect of capsaicin, which might be highly relevant for CIDP patients.

Highlights

Acute inflammatory demyelinating polyneuropathy (AIDP)/Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are inflammatory diseases of the peripheral nervous system (PNS)
Intrathecal transplantation of capsaicin-treated Schwann cells in the experimental autoimmune neuritis animal model In vivo study design We evaluated the isolated influence of naïve and capsaicin-treated SC in the EAN model
There was a significant toxicity of 1 mM capsaicin dissolved in dimethyl sulfoxide (DMSO) compared to a medium control in a 24-h incubation time via propidium iodide (PI) staining (Fig. 2, one-way analysis of variance (ANOVA) combined with KruskalWallis test, n = 5–16, p < 0.01)

Summary

Introduction

Acute inflammatory demyelinating polyneuropathy (AIDP)/Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are inflammatory diseases of the peripheral nervous system (PNS). The prevalence of CIDP ranges from 0.8 to 8.9 cases of 100,000 population depending on geographical region. Clinical features of GBS and CIDP are tetraparesis, sensory deficits, and areflexia. Despite immune treatment with intravenous immunoglobulins, corticosteroids, and plasma exchange, more than 25% of CIDP patients remain disabled with a severe impairment of sensorimotor function [4]. GBS and CIDP are characterized by a dysregulated autoimmune response resulting among others in an inflammation of the peripheral nerves, oxidative stress, Schwann cell (SC) apoptosis, and demyelination [5]. Few studies describe the impact of nutritive factors on chronic inflammatory demyelinating polyneuropathy (CIDP), an inflammatory disease of the peripheral nervous system. Its anti-inflammatory effect in the animal model experimental autoimmune neuritis (EAN) has been previously demonstrated

Methods

Results

Discussion

Conclusion