Effects of Lactobacillus casei Strain T2 (IBRC-M10783) on the Modulation of Th17/Treg and Evaluation of miR-155, miR-25, and IDO-1 Expression in a Cuprizone-Induced C57BL/6 Mouse Model of Demyelination

Inflammation. 2021 Feb;44(1):334-343. doi: 10.1007/s10753-020-01339-1. Epub 2020 Sep 10.

Abstract

Multiple sclerosis (MS) is a complex inflammatory disease in which demyelination occurs in the central nervous system affecting approximately 2.5 million people worldwide. Recent reports have shown that the gut microbiome plays a crucial role in the functioning of the immune system in inflammatory diseases such as MS. In this study, the cuprizone-induced demyelination mouse model was used to investigate the effect of Lactobacillus casei strain T2 (IBRC-M10783) on the alleviation of these mice. Female C57BL/6 mice (8-10 weeks old) were divided into 6 groups: group 1, normal control; group 2, cuprizone control (oral administration of cuprizone 0.2% w/w for 4 weeks); group 3, probiotic control (oral administration of 1 × 109 CFU/ml probiotic for 4 weeks); group 4, treatment 1 (probiotic for 4 weeks then cuprizone for 4 weeks); group 5, treatment 2 (cuprizone for 4 weeks then probiotic for 4 weeks); and group 6, treatment 3 (cuprizone for 4 weeks then probiotic for 4 weeks with vitamin D3 at a dose of 20 IU/day). Then, TGF-β and IL-17 were measured by ELISA, and the expression of miR-155, miR-25, and IDO-1 was evaluated by real-time PCR. Among the measured microRNAs, the results showed that there was a significant decrease in miR-155 expression between the treatment 1 group and the cuprizone group. In the case of IL-17, the results also showed a significant reduction between the three treatment groups and the cuprizone group. These observations suggest that L. casei can reduce proinflammatory cytokines and reduce demyelinating symptoms in the mouse model.

Keywords: IL-17; Lactobacillus casei strain T2 (IBRC-M10783); TGF-β; cuprizone; indoleamine-2,3-dioxygenase (IDO); miR-155; miR-25.

MeSH terms

  • Animals
  • Cuprizone / toxicity
  • Demyelinating Diseases / chemically induced
  • Demyelinating Diseases / metabolism*
  • Demyelinating Diseases / therapy
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / biosynthesis*
  • Lacticaseibacillus casei*
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / biosynthesis*
  • Probiotics / administration & dosage
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / metabolism*
  • Th17 Cells / drug effects
  • Th17 Cells / metabolism*

Substances

  • IDO1 protein, mouse
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • MIRN25 microRNA, mouse
  • MicroRNAs
  • Mirn155 microRNA, mouse
  • Cuprizone