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Vitamin D₃ and monomethyl fumarate enhance natural killer cell lysis of dendritic cells and ameliorate the clinical score in mice suffering from experimental autoimmune encephalomyelitis.

Al-Jaderi Z, Maghazachi AA - Toxins (Basel) (2015)

Bottom Line: The effect of treating these mice with 1α,25-Dihydroxyvitamin D₃ (vitamin D₃), or with monomethyl fumarate (MMF) was then examined.These findings were corroborated with isolating natural killer (NK) cells from vitamin D₃-treated or MMF-treated EAE mice that lysed immature or mature dendritic cells.The results support and extend other findings indicating that an important mechanism of action for drugs used to treat multiple sclerosis (MS) is to enhance NK cell lysis of dendritic cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, POB 1103, Oslo N-0317, Norway. al-jaderi@medisin.uio.no.

ABSTRACT
Experimental autoimmune encephalomyelitis (EAE) is a CD4⁺ T cell mediated inflammatory demyelinating disease that is induced in mice by administration of peptides derived from myelin proteins. We developed EAE in SJL mice by administration of PLP139-151 peptide. The effect of treating these mice with 1α,25-Dihydroxyvitamin D₃ (vitamin D₃), or with monomethyl fumarate (MMF) was then examined. We observed that both vitamin D₃ and MMF inhibited and/or prevented EAE in these mice. These findings were corroborated with isolating natural killer (NK) cells from vitamin D₃-treated or MMF-treated EAE mice that lysed immature or mature dendritic cells. The results support and extend other findings indicating that an important mechanism of action for drugs used to treat multiple sclerosis (MS) is to enhance NK cell lysis of dendritic cells.

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Comparison of the experimental autoimmune encephalomyelitis (EAE) clinical score among untreated mice (red line), mice treated with vitamin D3 (green line) or those fed MMF (pink line) for 50 days. The significant values were calculated using one way ANOVA followed by Sidak’s multiple comparison test during the entire period of the experiments (A). Results were also evaluated by area under curve analysis (B). Data were collected from 10 mice in each group at any time point.
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toxins-07-04730-f002: Comparison of the experimental autoimmune encephalomyelitis (EAE) clinical score among untreated mice (red line), mice treated with vitamin D3 (green line) or those fed MMF (pink line) for 50 days. The significant values were calculated using one way ANOVA followed by Sidak’s multiple comparison test during the entire period of the experiments (A). Results were also evaluated by area under curve analysis (B). Data were collected from 10 mice in each group at any time point.

Mentions: First we sought to demonstrate if injecting the mice with vitamin D3 or feeding them with MMF might reduce the incidence of EAE. During the 50 days of measuring the EAE clinical score, it was observed that injecting vitamin D3 significantly reduced the EAE clinical score in these mice (P < 0.01, Figure 2). However, the best reduction in the EAE clinical score was observed in mice fed with MMF (P < 0.0001 as compared to EAE mice that were left untreated, Figure 2A). Similar outcome was observed when the data were evaluated by area under curve analysis (Figure 2B).


Vitamin D₃ and monomethyl fumarate enhance natural killer cell lysis of dendritic cells and ameliorate the clinical score in mice suffering from experimental autoimmune encephalomyelitis.

Al-Jaderi Z, Maghazachi AA - Toxins (Basel) (2015)

Comparison of the experimental autoimmune encephalomyelitis (EAE) clinical score among untreated mice (red line), mice treated with vitamin D3 (green line) or those fed MMF (pink line) for 50 days. The significant values were calculated using one way ANOVA followed by Sidak’s multiple comparison test during the entire period of the experiments (A). Results were also evaluated by area under curve analysis (B). Data were collected from 10 mice in each group at any time point.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663530&req=5

toxins-07-04730-f002: Comparison of the experimental autoimmune encephalomyelitis (EAE) clinical score among untreated mice (red line), mice treated with vitamin D3 (green line) or those fed MMF (pink line) for 50 days. The significant values were calculated using one way ANOVA followed by Sidak’s multiple comparison test during the entire period of the experiments (A). Results were also evaluated by area under curve analysis (B). Data were collected from 10 mice in each group at any time point.
Mentions: First we sought to demonstrate if injecting the mice with vitamin D3 or feeding them with MMF might reduce the incidence of EAE. During the 50 days of measuring the EAE clinical score, it was observed that injecting vitamin D3 significantly reduced the EAE clinical score in these mice (P < 0.01, Figure 2). However, the best reduction in the EAE clinical score was observed in mice fed with MMF (P < 0.0001 as compared to EAE mice that were left untreated, Figure 2A). Similar outcome was observed when the data were evaluated by area under curve analysis (Figure 2B).

Bottom Line: The effect of treating these mice with 1α,25-Dihydroxyvitamin D₃ (vitamin D₃), or with monomethyl fumarate (MMF) was then examined.These findings were corroborated with isolating natural killer (NK) cells from vitamin D₃-treated or MMF-treated EAE mice that lysed immature or mature dendritic cells.The results support and extend other findings indicating that an important mechanism of action for drugs used to treat multiple sclerosis (MS) is to enhance NK cell lysis of dendritic cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, POB 1103, Oslo N-0317, Norway. al-jaderi@medisin.uio.no.

ABSTRACT
Experimental autoimmune encephalomyelitis (EAE) is a CD4⁺ T cell mediated inflammatory demyelinating disease that is induced in mice by administration of peptides derived from myelin proteins. We developed EAE in SJL mice by administration of PLP139-151 peptide. The effect of treating these mice with 1α,25-Dihydroxyvitamin D₃ (vitamin D₃), or with monomethyl fumarate (MMF) was then examined. We observed that both vitamin D₃ and MMF inhibited and/or prevented EAE in these mice. These findings were corroborated with isolating natural killer (NK) cells from vitamin D₃-treated or MMF-treated EAE mice that lysed immature or mature dendritic cells. The results support and extend other findings indicating that an important mechanism of action for drugs used to treat multiple sclerosis (MS) is to enhance NK cell lysis of dendritic cells.

Show MeSH
Related in: MedlinePlus