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Immunomodulatory and anti-oxidative effect of the direct TRPV1 receptor agonist capsaicin on Schwann cells.
Journal of Neuroinflammation ( IF 9.3 ) Pub Date : 2020-05-06 , DOI: 10.1186/s12974-020-01821-5
Thomas Grüter 1 , Alina Blusch 1 , Jeremias Motte 1 , Melissa Sgodzai 1 , Hussein Bachir 1 , Rafael Klimas 1 , Björn Ambrosius 1 , Ralf Gold 1 , Gisa Ellrichmann 1 , Kalliopi Pitarokoili 1
Affiliation  

BACKGROUND Only 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. METHODS In 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. RESULTS In 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. CONCLUSIONS In 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.

中文翻译:

直接TRPV1受体激动剂辣椒素对雪旺细胞的免疫调节和抗氧化作用。

背景技术只有很少的研究描述了营养因素对慢性炎性脱髓鞘性多发性神经病(CIDP)的影响,CIDP是周围神经系统的炎性疾病。辣椒的活性成分辣椒素是瞬时受体潜在通道香草样亚家族成员1的直接激动剂。其在动物模型实验性自身免疫性神经炎(EAN)中的抗炎作用已得到证明。方法在本研究中,我们描述了辣椒素在体外对雪旺细胞(SCs)的抗炎和抗氧化作用。因此,我们分析了辣椒素对雪旺细胞的基因表达模式,主要组织相容性复合物II类(MHC-II)呈递和H2O2诱导的氧化应激的影响。此外,通过髓鞘碱性蛋白染色,在SC背根神经节(DRG)共培养物中检查了辣椒素对髓鞘形成的影响。最后,为了研究辣椒素对EAN病理学中SC的分离作用,我们在EAN免疫大鼠中鞘内移植了朴素和辣椒素预处理的SC,并分析了临床表现,电生理参数和坐骨神经中的细胞因子表达。结果在SC单培养中,与辣椒素一起孵育显着降低了干扰素γ诱导的MHC-II产生以及toll样受体4和细胞间粘附分子1 mRNA的表达。辣椒素处理后,降钙素基因相关肽mRNA的产生明显上调。辣椒素可在预防性而非治疗性环境中降低H2O2诱导的SC氧化应激。在SC-DRG共培养中,辣椒素不影响髓鞘形成率。在经EAN免疫的大鼠中进行鞘内初始幼稚和辣椒素预处理的SC移植后,幼稚但未进行辣椒素预处理的鞘内SC移植改善了大鼠的EAN病理。结论总之,我们能够通过减少抗原呈递和表达抗炎药来证明辣椒素在SC培养物中具有直接的免疫调节和抗氧化作用。此外,辣椒素增加了SC对氧化应激的抵抗力。辣椒素对髓鞘形成的主要作用尚未得到证实。这些结果与以前的数据一致,后者显示了辣椒素的抗炎作用,这可能与CIDP患者高度相关。在经EAN免疫的大鼠中进行鞘内幼稚和辣椒素预处理的SC移植后,幼稚但未进行辣椒素预处理的鞘内SC移植改善了大鼠的EAN病理。结论总之,我们能够通过减少抗原呈递和表达抗炎药来证明辣椒素在SC培养物中具有直接的免疫调节和抗氧化作用。此外,辣椒素增加了SC对氧化应激的抵抗力。辣椒素对髓鞘形成的主要作用尚未得到证实。这些结果与以前的数据一致,后者显示了辣椒素的抗炎作用,这可能与CIDP患者高度相关。在经EAN免疫的大鼠中进行鞘内初始幼稚和辣椒素预处理的SC移植后,幼稚但未进行辣椒素预处理的鞘内SC移植改善了大鼠的EAN病理。结论总之,我们能够通过减少抗原呈递和表达抗炎药来证明辣椒素在SC培养物中具有直接的免疫调节和抗氧化作用。此外,辣椒素增加了SC对氧化应激的抵抗力。辣椒素对髓鞘形成的主要作用尚未得到证实。这些结果与以前的数据一致,后者显示了辣椒素的抗炎作用,这可能与CIDP患者高度相关。我们能够通过减少抗原呈递和抗炎性表达来证明辣椒素在SC培养物中具有直接的免疫调节和抗氧化作用。此外,辣椒素增加了SC对氧化应激的抵抗力。辣椒素对髓鞘形成的主要作用尚未得到证实。这些结果与以前的数据一致,后者显示了辣椒素的抗炎作用,这可能与CIDP患者高度相关。我们能够通过减少抗原呈递和抗炎性表达来证明辣椒素在SC培养物中具有直接的免疫调节和抗氧化作用。此外,辣椒素增加了SC对氧化应激的抵抗力。辣椒素对髓鞘形成的主要作用尚未得到证实。这些结果与以前的数据一致,后者显示了辣椒素的抗炎作用,这可能与CIDP患者高度相关。
更新日期:2020-05-06
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