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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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Related in: MedlinePlus

An overview of the study design. Mice were inoculated at day 0 with antigen and pertussis toxin (PTX). They were either left untreated or were treated with vitamin D3 at the indicated time points (blue arrows), or were fed with monomethyl fumarate (MMF) every day throughout the study. After 7 days, bone marrow was harvested to generate immature dendritic cells (iDCs) and mature dendritic cells (mDCs). At day 15 the spleens were isolated to generate natural killer (NK) cells which were used in the cytotoxicity assay.
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toxins-07-04730-f001: An overview of the study design. Mice were inoculated at day 0 with antigen and pertussis toxin (PTX). They were either left untreated or were treated with vitamin D3 at the indicated time points (blue arrows), or were fed with monomethyl fumarate (MMF) every day throughout the study. After 7 days, bone marrow was harvested to generate immature dendritic cells (iDCs) and mature dendritic cells (mDCs). At day 15 the spleens were isolated to generate natural killer (NK) cells which were used in the cytotoxicity assay.

Mentions: The protocol for the study design is shown in Figure 1. EAE was induced in SJL mice, and as a control normal mice were used. The first group of mice was left untreated, while the second was treated with vitamin D3, and the third group was fed with MMF, as shown in Figure 1.


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)

An overview of the study design. Mice were inoculated at day 0 with antigen and pertussis toxin (PTX). They were either left untreated or were treated with vitamin D3 at the indicated time points (blue arrows), or were fed with monomethyl fumarate (MMF) every day throughout the study. After 7 days, bone marrow was harvested to generate immature dendritic cells (iDCs) and mature dendritic cells (mDCs). At day 15 the spleens were isolated to generate natural killer (NK) cells which were used in the cytotoxicity assay.
© Copyright Policy
Related In: Results  -  Collection

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

toxins-07-04730-f001: An overview of the study design. Mice were inoculated at day 0 with antigen and pertussis toxin (PTX). They were either left untreated or were treated with vitamin D3 at the indicated time points (blue arrows), or were fed with monomethyl fumarate (MMF) every day throughout the study. After 7 days, bone marrow was harvested to generate immature dendritic cells (iDCs) and mature dendritic cells (mDCs). At day 15 the spleens were isolated to generate natural killer (NK) cells which were used in the cytotoxicity assay.
Mentions: The protocol for the study design is shown in Figure 1. EAE was induced in SJL mice, and as a control normal mice were used. The first group of mice was left untreated, while the second was treated with vitamin D3, and the third group was fed with MMF, as shown in Figure 1.

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