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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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MMF reduces the EAE clinical score and enhances NK cell lysis of DCs. EAE clinical score in mice gavaged MMF (pink line), or control mice treated similarly to MMF-gavaged mice, except that vehicle was used instead of MMF (red line) (A). Body weights of mice treated with MMF (pink line), untreated EAE mice (red lines), or normal mice where no disease was induced (blue line) are shown (B). MMF treatment increases NK cell lysis of iDCs (C) or mDCs (D). E:T ratio is 50:1. Significant values were calculated using one-way ANOVA. * P < 0.05.
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toxins-07-04730-f004: MMF reduces the EAE clinical score and enhances NK cell lysis of DCs. EAE clinical score in mice gavaged MMF (pink line), or control mice treated similarly to MMF-gavaged mice, except that vehicle was used instead of MMF (red line) (A). Body weights of mice treated with MMF (pink line), untreated EAE mice (red lines), or normal mice where no disease was induced (blue line) are shown (B). MMF treatment increases NK cell lysis of iDCs (C) or mDCs (D). E:T ratio is 50:1. Significant values were calculated using one-way ANOVA. * P < 0.05.

Mentions: The effects of treatment with MMF on EAE clinical score and body weight are shown in Figure 3. The results confirmed those observed earlier using 10 mice from each group (see Figure 2). The disease started to develop after about 6 days of initiation in untreated mice. However, there was a delay in EAE clinical score until day 12 in mice gavaged with MMF. Further, there was a continuous reduction in the EAE clinical score in mice fed MMF throughout the 50 days of measuring the disease score in these mice (Figure 4A). Surprisingly, mice fed MMF gained weight throughout the study hence, the weight of these mice was much higher than normal mice (Figure 4B). In contrast, mice suffering from EAE which were not treated with the drug lost weight compared to normal mice or mice treated with MMF (Figure 4B). To correlate these findings with activating NK cell lysis of DCs, we isolated NK cells from MMF fed mice and from untreated mice as well as from normal mice. A clear and significant enhancement of NK cell lysis against iDCs was observed in mice fed with MMF (P < 0.05, Figure 4C). Similarly, treatment with MMF significantly augmented NK cell lysis of mDCs in mice suffering from EAE (P < 0.05 as compared to untreated EAE mice, Figure 4D).


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)

MMF reduces the EAE clinical score and enhances NK cell lysis of DCs. EAE clinical score in mice gavaged MMF (pink line), or control mice treated similarly to MMF-gavaged mice, except that vehicle was used instead of MMF (red line) (A). Body weights of mice treated with MMF (pink line), untreated EAE mice (red lines), or normal mice where no disease was induced (blue line) are shown (B). MMF treatment increases NK cell lysis of iDCs (C) or mDCs (D). E:T ratio is 50:1. Significant values were calculated using one-way ANOVA. * P < 0.05.
© Copyright Policy
Related In: Results  -  Collection

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

toxins-07-04730-f004: MMF reduces the EAE clinical score and enhances NK cell lysis of DCs. EAE clinical score in mice gavaged MMF (pink line), or control mice treated similarly to MMF-gavaged mice, except that vehicle was used instead of MMF (red line) (A). Body weights of mice treated with MMF (pink line), untreated EAE mice (red lines), or normal mice where no disease was induced (blue line) are shown (B). MMF treatment increases NK cell lysis of iDCs (C) or mDCs (D). E:T ratio is 50:1. Significant values were calculated using one-way ANOVA. * P < 0.05.
Mentions: The effects of treatment with MMF on EAE clinical score and body weight are shown in Figure 3. The results confirmed those observed earlier using 10 mice from each group (see Figure 2). The disease started to develop after about 6 days of initiation in untreated mice. However, there was a delay in EAE clinical score until day 12 in mice gavaged with MMF. Further, there was a continuous reduction in the EAE clinical score in mice fed MMF throughout the 50 days of measuring the disease score in these mice (Figure 4A). Surprisingly, mice fed MMF gained weight throughout the study hence, the weight of these mice was much higher than normal mice (Figure 4B). In contrast, mice suffering from EAE which were not treated with the drug lost weight compared to normal mice or mice treated with MMF (Figure 4B). To correlate these findings with activating NK cell lysis of DCs, we isolated NK cells from MMF fed mice and from untreated mice as well as from normal mice. A clear and significant enhancement of NK cell lysis against iDCs was observed in mice fed with MMF (P < 0.05, Figure 4C). Similarly, treatment with MMF significantly augmented NK cell lysis of mDCs in mice suffering from EAE (P < 0.05 as compared to untreated EAE mice, Figure 4D).

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