Montelukast alleviates inflammation in experimental autoimmune encephalomyelitis by altering Th17 differentiation in a mouse model.

Montelukast is a leukotriene receptor antagonist that is known to prevent allergic rhinitis and asthma. Blocking the Cysteinyl leukotriene receptor (CysLTR1), one of the primary receptors of leukotrienes, has been demonstrated to be efficacious in ameliorating experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), through disrupting chemotaxis of infiltrating T cells. However, the role of CysLTR1 in the pathogenesis of MS is not well understood. Here, we show that MS patients had higher expression of CysLTR1 in the circulation and central nervous system (CNS). The majority of CD4+ T cells expressed CysLTR1 in MS lesions. Among T-cell subsets, Th17 cells had the highest expression of CysLTR1, and blocking CysLTR1 signalling abrogated their development in vitro. Inhibition of CysLTR1 by montelukast suppressed EAE development in both a prophylactic and therapeutic manner and inhibited myelin loss in EAE mice. Similarly, the in vivo results showed that montelukast inhibited Th17 response in EAE mice and that Th17 cells treated with montelukast had reduced encephalitogenic in adoptive EAE. Our findings strongly suggest that targeting Th17 response by inhibiting CysLTR1 signalling could be a promising therapeutic strategy for the treatment of MS and CNS inflammatory diseases.

Generation of Oligodendrocyte Progenitor Cells From Mouse Bone Marrow Cells.

Oligodendrocyte progenitor cells (OPCs) are a subtype of glial cells responsible for myelin regeneration. Oligodendrocytes (OLGs) originate from OPCs and are the myelinating cells in the central nervous system (CNS). OLGs play an important role in the context of lesions in which myelin loss occurs. Even though many protocols for isolating OPCs have been published, their cellular yield remains a limit for clinical application. The protocol proposed here is novel and has practical value; in fact, OPCs can be generated from a source of autologous cells without gene manipulation. Our method represents a rapid, and high-efficiency differentiation protocol for generating mouse OLGs from bone marrow-derived cells using growth-factor defined media. With this protocol, it is possible to obtain mature OLGs in 7-8 weeks. Within 2-3 weeks from bone marrow (BM) isolation, after neurospheres formed, the cells differentiate into Nestin+ Sox2+ neural stem cells (NSCs), around 30 days. OPCs specific markers start to be expressed around day 38, followed by RIP+O4+ around day 42. CNPase+ mature OLGs are finally obtained around 7-8 weeks. Further, bone marrow-derived OPCs exhibited therapeutic effect in shiverer (Shi) mice, promoting myelin regeneration and reducing the tremor. Here, we propose a method by which OLGs can be generated starting from BM cells and have similar abilities to subventricular zone (SVZ)-derived cells. This protocol significantly decreases the timing and costs of the OLGs differentiation within 2 months of culture.

Nutshell Extracts of Xanthoceras sorbifolia: A New Potential Source of Bioactive Phenolic Compounds as a Natural Antioxidant and Immunomodulator.

The nutshell of Xanthoceras sorbifolia, a waste product in the production of edible oil, is rich in health-promoting phenolic acids. However, the individual constituents, bioactivities, and mechanism of action are largely unknown. In this study, 20 phenolic compounds were characterized in nutshell extract (NE) of X. sorbifolia by gas chromatography-mass spectrometry. Four established in vitro studies showed that NE has significant antioxidant potential. Results in vivo indicated that oral administration of NE effectively ameliorated clinical disease severity of experimental autoimmune encephalomyelitis (EAE) and reduced the neuroinflammation and the central nervous system (CNS) demyelination. The underlying mechanism of NE-induced effects involved decreased penetration of pathogenic immunocyte into the CNS, a reduced production of proinflammatory cytokines and factors, and suppressed differentiation of type 1 T helper and type 17 T helper cells through the Janus kinase/signal transducer and activator of transcription pathway. Taken together, our studies showed that X. sorbifolia nutshell, considered a waste material in the food industry, is a novel source of a natural antioxidant and immunomodulator.