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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

Effect of treating mice with vitamin D3 or MMF on the expression of various molecules on the surface of DCs. iDCs or mDCs were isolated from normal untreated mice, EAE mice, EAE mice injected IP with vitamin D3 or mice orally fed MMF. These cells were labeled with antibodies towards CD80, CD205 or E-cadherin and then examined in the flow cytometry. Mean ± SEM of three experiments except for E-cadherin in mDCs where only two experiments were performed.
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toxins-07-04730-f005: Effect of treating mice with vitamin D3 or MMF on the expression of various molecules on the surface of DCs. iDCs or mDCs were isolated from normal untreated mice, EAE mice, EAE mice injected IP with vitamin D3 or mice orally fed MMF. These cells were labeled with antibodies towards CD80, CD205 or E-cadherin and then examined in the flow cytometry. Mean ± SEM of three experiments except for E-cadherin in mDCs where only two experiments were performed.

Mentions: It was previously reported that MMF affects DCs differentiation [31], or monocyte polarization [32]. To investigate whether enhancing NK cell lysis of DCs might be due to changes in DCs phenotypic expression, we examined the expression of various surface molecules in iDCs and mDCs isolated from normal mice, mice with EAE, mice with EAE injected with vitamin D3, or mice with EAE fed MMF. We chose three molecules important for DCs maturation; these included the co-stimulatory molecule CD80, recognition and adhesion molecules CD205 and E-cadherin [33]. We observed no significant effects on the expression of CD80 molecule in iDCs (Figure 5A), or mDCs (Figure 5B), after treating the mice with vitamin D3 or MMF. No effect on the expression of CD205 was seen in iDCs (Figure 5A), but vitamin D3 treatment reduced the expression of this molecule on the surface of mDCs (Figure 5B). E-cadherin expression was up-regulated in EAE mice, and that both vitamin D3 and MMF reversed this up-regulation on iDCs (Figure 5A). However, no effect of treatments on E-cadherin was observed in mDCs (Figure 5B).


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)

Effect of treating mice with vitamin D3 or MMF on the expression of various molecules on the surface of DCs. iDCs or mDCs were isolated from normal untreated mice, EAE mice, EAE mice injected IP with vitamin D3 or mice orally fed MMF. These cells were labeled with antibodies towards CD80, CD205 or E-cadherin and then examined in the flow cytometry. Mean ± SEM of three experiments except for E-cadherin in mDCs where only two experiments were performed.
© Copyright Policy
Related In: Results  -  Collection

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

toxins-07-04730-f005: Effect of treating mice with vitamin D3 or MMF on the expression of various molecules on the surface of DCs. iDCs or mDCs were isolated from normal untreated mice, EAE mice, EAE mice injected IP with vitamin D3 or mice orally fed MMF. These cells were labeled with antibodies towards CD80, CD205 or E-cadherin and then examined in the flow cytometry. Mean ± SEM of three experiments except for E-cadherin in mDCs where only two experiments were performed.
Mentions: It was previously reported that MMF affects DCs differentiation [31], or monocyte polarization [32]. To investigate whether enhancing NK cell lysis of DCs might be due to changes in DCs phenotypic expression, we examined the expression of various surface molecules in iDCs and mDCs isolated from normal mice, mice with EAE, mice with EAE injected with vitamin D3, or mice with EAE fed MMF. We chose three molecules important for DCs maturation; these included the co-stimulatory molecule CD80, recognition and adhesion molecules CD205 and E-cadherin [33]. We observed no significant effects on the expression of CD80 molecule in iDCs (Figure 5A), or mDCs (Figure 5B), after treating the mice with vitamin D3 or MMF. No effect on the expression of CD205 was seen in iDCs (Figure 5A), but vitamin D3 treatment reduced the expression of this molecule on the surface of mDCs (Figure 5B). E-cadherin expression was up-regulated in EAE mice, and that both vitamin D3 and MMF reversed this up-regulation on iDCs (Figure 5A). However, no effect of treatments on E-cadherin was observed in mDCs (Figure 5B).

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