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Antigen exposure in the late light period induces severe symptoms of food allergy in an OVA-allergic mouse model.

Tanabe K, Kitagawa E, Wada M, Haraguchi A, Orihara K, Tahara Y, Nakao A, Shibata S - Sci Rep (2015)

Bottom Line: The light period group showed higher allergic diarrhea and weight loss than the dark period group.The production of type 2 cytokines, IL-13 and IL-5, from the mesenteric lymph nodes and ovalbumin absorption was higher in the light period group than in the dark period group.Compared to the dark period group, the mRNA expression levels of the tight junction proteins were lower in the light period group.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.

ABSTRACT
The mammalian circadian clock controls many physiological processes that include immune responses and allergic reactions. Several studies have investigated the circadian regulation of intestinal permeability and tight junctions known to be affected by cytokines. However, the contribution of circadian clock to food allergy symptoms remains unclear. Therefore, we investigated the role of the circadian clock in determining the severity of food allergies. We prepared an ovalbumin food allergy mouse model, and orally administered ovalbumin either late in the light or late in the dark period under light-dark cycle. The light period group showed higher allergic diarrhea and weight loss than the dark period group. The production of type 2 cytokines, IL-13 and IL-5, from the mesenteric lymph nodes and ovalbumin absorption was higher in the light period group than in the dark period group. Compared to the dark period group, the mRNA expression levels of the tight junction proteins were lower in the light period group. We have demonstrated that increased production of type 2 cytokines and intestinal permeability in the light period induced severe food allergy symptoms. Our results suggest that the time of food antigen intake might affect the determination of the severity of food allergy symptoms.

No MeSH data available.


Related in: MedlinePlus

Mice orally administered ovalbumin (OVA) in the light period had more severe local allergic reactions.(a) Immunization schedule for the experiment. Female intact or SCN lesioned BALB/c mice were sensitized and subsequently treated with orally administered OVA (80 mg/500 μl distilled water) in the light period or the dark period. (b) The diarrhea score was assessed 30–60 min after treatment in intact mice. (c) Body weight was measured before and after treatment in intact mice. The pre-treatment body weight was subtracted from the post-treatment body weight. (d) Significant correlation between the diarrhea score and change in body weight. The data from each individual in the first and the second challenges are plotted. *p < 0.05. Spearman’s rank correlation coefficient was calculated to assess correlation. (e) The diarrhea score was assessed 30–60 min after treatment in SCN lesion mice. (f) Body weight was measured before and after treatment in SCN lesion mice. The pre-treatment body weight was subtracted from the post-treatment body weight. The data (e,f) are presented as the means ± SEM (n = 10). (g) An increase in OVA-specific serum levels of IgE, in intact mice measured by ELISA. (h) The mRNA expression levels in the jejunum were measured using real-time RT-PCR. The data (b,c,g) are presented as the means ± SEM (n = 9–10). Data (b,c) *p < 0.05, **p < 0.01 in the light period versus the dark period calculated with a t-test. $p < 0.05 for the light period of first challenge versus the light period of second, calculated with a Wilcoxon signed-rank test. #p < 0.05 for the dark period of the first challenge versus the dark period of the second challenge, calculated with a t-test. Data (g) $p < 0.05 pre-treatment versus post-treatment calculated with a Wilcoxon signed-rank test. The data (h) are presented as means ± SEM (n = 7–10). ***p < 0.001, *p < 0.05 for light period versus dark period, calculated with a Mann-Whitney test.
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f1: Mice orally administered ovalbumin (OVA) in the light period had more severe local allergic reactions.(a) Immunization schedule for the experiment. Female intact or SCN lesioned BALB/c mice were sensitized and subsequently treated with orally administered OVA (80 mg/500 μl distilled water) in the light period or the dark period. (b) The diarrhea score was assessed 30–60 min after treatment in intact mice. (c) Body weight was measured before and after treatment in intact mice. The pre-treatment body weight was subtracted from the post-treatment body weight. (d) Significant correlation between the diarrhea score and change in body weight. The data from each individual in the first and the second challenges are plotted. *p < 0.05. Spearman’s rank correlation coefficient was calculated to assess correlation. (e) The diarrhea score was assessed 30–60 min after treatment in SCN lesion mice. (f) Body weight was measured before and after treatment in SCN lesion mice. The pre-treatment body weight was subtracted from the post-treatment body weight. The data (e,f) are presented as the means ± SEM (n = 10). (g) An increase in OVA-specific serum levels of IgE, in intact mice measured by ELISA. (h) The mRNA expression levels in the jejunum were measured using real-time RT-PCR. The data (b,c,g) are presented as the means ± SEM (n = 9–10). Data (b,c) *p < 0.05, **p < 0.01 in the light period versus the dark period calculated with a t-test. $p < 0.05 for the light period of first challenge versus the light period of second, calculated with a Wilcoxon signed-rank test. #p < 0.05 for the dark period of the first challenge versus the dark period of the second challenge, calculated with a t-test. Data (g) $p < 0.05 pre-treatment versus post-treatment calculated with a Wilcoxon signed-rank test. The data (h) are presented as means ± SEM (n = 7–10). ***p < 0.001, *p < 0.05 for light period versus dark period, calculated with a Mann-Whitney test.

Mentions: We investigated whether the symptoms of food allergies differed in severity when the time of the oral treatment was changed. Mice were orally administered OVA in the late light period (light period group) or in the late dark period (dark period group). The overall diarrhea score was higher in the light period group than the dark period group in both the first and the second challenges (Fig. 1b). Accompanied with the diarrhea, most of the mice lost weight. The light period group lost significantly more weight than the dark period group (Fig. 1c). Furthermore, the diarrhea score showed a negative correlation with body weight change (Fig. 1d). To investigate the link between the circadian clock and food allergy, OVA sensitized SCN lesioned mice27 as a circadian disruption mouse model were challenged with OVA. OVA-specific serum IgE before OVA challenge in SCN lesioned mice was comparable with that in intact mice (data not shown). Significant differences of diarrhea score and body weight change that were seen between the light period and the dark period groups disappeared when mice had lesioned SCN (Fig. 1e,f). This result suggests that SCN, which generates the circadian rhythm, regulates the severity of food allergy symptoms, and that the timing of food-antigen intake is one of the factors that determine the severity of food allergic diarrhea.


Antigen exposure in the late light period induces severe symptoms of food allergy in an OVA-allergic mouse model.

Tanabe K, Kitagawa E, Wada M, Haraguchi A, Orihara K, Tahara Y, Nakao A, Shibata S - Sci Rep (2015)

Mice orally administered ovalbumin (OVA) in the light period had more severe local allergic reactions.(a) Immunization schedule for the experiment. Female intact or SCN lesioned BALB/c mice were sensitized and subsequently treated with orally administered OVA (80 mg/500 μl distilled water) in the light period or the dark period. (b) The diarrhea score was assessed 30–60 min after treatment in intact mice. (c) Body weight was measured before and after treatment in intact mice. The pre-treatment body weight was subtracted from the post-treatment body weight. (d) Significant correlation between the diarrhea score and change in body weight. The data from each individual in the first and the second challenges are plotted. *p < 0.05. Spearman’s rank correlation coefficient was calculated to assess correlation. (e) The diarrhea score was assessed 30–60 min after treatment in SCN lesion mice. (f) Body weight was measured before and after treatment in SCN lesion mice. The pre-treatment body weight was subtracted from the post-treatment body weight. The data (e,f) are presented as the means ± SEM (n = 10). (g) An increase in OVA-specific serum levels of IgE, in intact mice measured by ELISA. (h) The mRNA expression levels in the jejunum were measured using real-time RT-PCR. The data (b,c,g) are presented as the means ± SEM (n = 9–10). Data (b,c) *p < 0.05, **p < 0.01 in the light period versus the dark period calculated with a t-test. $p < 0.05 for the light period of first challenge versus the light period of second, calculated with a Wilcoxon signed-rank test. #p < 0.05 for the dark period of the first challenge versus the dark period of the second challenge, calculated with a t-test. Data (g) $p < 0.05 pre-treatment versus post-treatment calculated with a Wilcoxon signed-rank test. The data (h) are presented as means ± SEM (n = 7–10). ***p < 0.001, *p < 0.05 for light period versus dark period, calculated with a Mann-Whitney test.
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Related In: Results  -  Collection

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f1: Mice orally administered ovalbumin (OVA) in the light period had more severe local allergic reactions.(a) Immunization schedule for the experiment. Female intact or SCN lesioned BALB/c mice were sensitized and subsequently treated with orally administered OVA (80 mg/500 μl distilled water) in the light period or the dark period. (b) The diarrhea score was assessed 30–60 min after treatment in intact mice. (c) Body weight was measured before and after treatment in intact mice. The pre-treatment body weight was subtracted from the post-treatment body weight. (d) Significant correlation between the diarrhea score and change in body weight. The data from each individual in the first and the second challenges are plotted. *p < 0.05. Spearman’s rank correlation coefficient was calculated to assess correlation. (e) The diarrhea score was assessed 30–60 min after treatment in SCN lesion mice. (f) Body weight was measured before and after treatment in SCN lesion mice. The pre-treatment body weight was subtracted from the post-treatment body weight. The data (e,f) are presented as the means ± SEM (n = 10). (g) An increase in OVA-specific serum levels of IgE, in intact mice measured by ELISA. (h) The mRNA expression levels in the jejunum were measured using real-time RT-PCR. The data (b,c,g) are presented as the means ± SEM (n = 9–10). Data (b,c) *p < 0.05, **p < 0.01 in the light period versus the dark period calculated with a t-test. $p < 0.05 for the light period of first challenge versus the light period of second, calculated with a Wilcoxon signed-rank test. #p < 0.05 for the dark period of the first challenge versus the dark period of the second challenge, calculated with a t-test. Data (g) $p < 0.05 pre-treatment versus post-treatment calculated with a Wilcoxon signed-rank test. The data (h) are presented as means ± SEM (n = 7–10). ***p < 0.001, *p < 0.05 for light period versus dark period, calculated with a Mann-Whitney test.
Mentions: We investigated whether the symptoms of food allergies differed in severity when the time of the oral treatment was changed. Mice were orally administered OVA in the late light period (light period group) or in the late dark period (dark period group). The overall diarrhea score was higher in the light period group than the dark period group in both the first and the second challenges (Fig. 1b). Accompanied with the diarrhea, most of the mice lost weight. The light period group lost significantly more weight than the dark period group (Fig. 1c). Furthermore, the diarrhea score showed a negative correlation with body weight change (Fig. 1d). To investigate the link between the circadian clock and food allergy, OVA sensitized SCN lesioned mice27 as a circadian disruption mouse model were challenged with OVA. OVA-specific serum IgE before OVA challenge in SCN lesioned mice was comparable with that in intact mice (data not shown). Significant differences of diarrhea score and body weight change that were seen between the light period and the dark period groups disappeared when mice had lesioned SCN (Fig. 1e,f). This result suggests that SCN, which generates the circadian rhythm, regulates the severity of food allergy symptoms, and that the timing of food-antigen intake is one of the factors that determine the severity of food allergic diarrhea.

Bottom Line: The light period group showed higher allergic diarrhea and weight loss than the dark period group.The production of type 2 cytokines, IL-13 and IL-5, from the mesenteric lymph nodes and ovalbumin absorption was higher in the light period group than in the dark period group.Compared to the dark period group, the mRNA expression levels of the tight junction proteins were lower in the light period group.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.

ABSTRACT
The mammalian circadian clock controls many physiological processes that include immune responses and allergic reactions. Several studies have investigated the circadian regulation of intestinal permeability and tight junctions known to be affected by cytokines. However, the contribution of circadian clock to food allergy symptoms remains unclear. Therefore, we investigated the role of the circadian clock in determining the severity of food allergies. We prepared an ovalbumin food allergy mouse model, and orally administered ovalbumin either late in the light or late in the dark period under light-dark cycle. The light period group showed higher allergic diarrhea and weight loss than the dark period group. The production of type 2 cytokines, IL-13 and IL-5, from the mesenteric lymph nodes and ovalbumin absorption was higher in the light period group than in the dark period group. Compared to the dark period group, the mRNA expression levels of the tight junction proteins were lower in the light period group. We have demonstrated that increased production of type 2 cytokines and intestinal permeability in the light period induced severe food allergy symptoms. Our results suggest that the time of food antigen intake might affect the determination of the severity of food allergy symptoms.

No MeSH data available.


Related in: MedlinePlus