Enhanced Anti-Allergic Activity of Milk Casein Phosphopeptide by Additional Phosphorylation in Ovalbumin-Sensitized Mice
The proteolytic digest of milk casein, known as casein phosphopeptide (CPP-III), exhibits diverse biological activities, including calcium absorption and antioxidant activities. We hypothesized that the additional phosphorylation of this peptide can enhance its immunomodulatory activity such as supp...
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| Published in | Molecules (Basel, Switzerland) Vol. 24; no. 4; p. 738 |
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| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
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19.02.2019
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| Abstract | The proteolytic digest of milk casein, known as casein phosphopeptide (CPP-III), exhibits diverse biological activities, including calcium absorption and antioxidant activities. We hypothesized that the additional phosphorylation of this peptide can enhance its immunomodulatory activity such as suppression of allergy-associated cytokine and antigen-specific immune response. This study was conducted to assess whether oral intake of additionally phosphorylated CPP-III (P-CPP) attenuates ovalbumin (OVA)-induced IgE-mediated allergic reactions because of the additional phosphate groups. Female BALB/c mice were intraperitoneally sensitized with OVA twice at intervals of 14 days and then orally fed native CPP-III (N-CPP), P-CPP, and dephosphorylated CPP-III (D-CPP) for 6 weeks. Next, the mice were orally challenged with 50 mg of OVA. Oral administration of P-CPP suppressed total and specific IgE levels in the serum. Mice fed P-CPP exhibited low levels of OVA-specific IgG1 and increased OVA-specific IgG2a. P-CPP also suppressed IL-4 production, while D-CPP showed similar a level compared to that of the control. Further, P-CPP increased the population of the T follicular helper (Tfh) cell in the spleen. These results suggest that additional phosphorylation of CPP can enhance the attenuation of allergen-specific IgE-modulated allergic reactions in a murine food allergy model. |
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| AbstractList | The proteolytic digest of milk casein, known as casein phosphopeptide (CPP-III), exhibits diverse biological activities, including calcium absorption and antioxidant activities. We hypothesized that the additional phosphorylation of this peptide can enhance its immunomodulatory activity such as suppression of allergy-associated cytokine and antigen-specific immune response. This study was conducted to assess whether oral intake of additionally phosphorylated CPP-III (P-CPP) attenuates ovalbumin (OVA)-induced IgE-mediated allergic reactions because of the additional phosphate groups. Female BALB/c mice were intraperitoneally sensitized with OVA twice at intervals of 14 days and then orally fed native CPP-III (N-CPP), P-CPP, and dephosphorylated CPP-III (D-CPP) for 6 weeks. Next, the mice were orally challenged with 50 mg of OVA. Oral administration of P-CPP suppressed total and specific IgE levels in the serum. Mice fed P-CPP exhibited low levels of OVA-specific IgG1 and increased OVA-specific IgG2a. P-CPP also suppressed IL-4 production, while D-CPP showed similar a level compared to that of the control. Further, P-CPP increased the population of the T follicular helper (Tfh) cell in the spleen. These results suggest that additional phosphorylation of CPP can enhance the attenuation of allergen-specific IgE-modulated allergic reactions in a murine food allergy model. The proteolytic digest of milk casein, known as casein phosphopeptide (CPP-III), exhibits diverse biological activities, including calcium absorption and antioxidant activities. We hypothesized that the additional phosphorylation of this peptide can enhance its immunomodulatory activity such as suppression of allergy-associated cytokine and antigen-specific immune response. This study was conducted to assess whether oral intake of additionally phosphorylated CPP-III (P-CPP) attenuates ovalbumin (OVA)-induced IgE-mediated allergic reactions because of the additional phosphate groups. Female BALB/c mice were intraperitoneally sensitized with OVA twice at intervals of 14 days and then orally fed native CPP-III (N-CPP), P-CPP, and dephosphorylated CPP-III (D-CPP) for 6 weeks. Next, the mice were orally challenged with 50 mg of OVA. Oral administration of P-CPP suppressed total and specific IgE levels in the serum. Mice fed P-CPP exhibited low levels of OVA-specific IgG1 and increased OVA-specific IgG2a. P-CPP also suppressed IL-4 production, while D-CPP showed similar a level compared to that of the control. Further, P-CPP increased the population of the T follicular helper (Tfh) cell in the spleen. These results suggest that additional phosphorylation of CPP can enhance the attenuation of allergen-specific IgE-modulated allergic reactions in a murine food allergy model.The proteolytic digest of milk casein, known as casein phosphopeptide (CPP-III), exhibits diverse biological activities, including calcium absorption and antioxidant activities. We hypothesized that the additional phosphorylation of this peptide can enhance its immunomodulatory activity such as suppression of allergy-associated cytokine and antigen-specific immune response. This study was conducted to assess whether oral intake of additionally phosphorylated CPP-III (P-CPP) attenuates ovalbumin (OVA)-induced IgE-mediated allergic reactions because of the additional phosphate groups. Female BALB/c mice were intraperitoneally sensitized with OVA twice at intervals of 14 days and then orally fed native CPP-III (N-CPP), P-CPP, and dephosphorylated CPP-III (D-CPP) for 6 weeks. Next, the mice were orally challenged with 50 mg of OVA. Oral administration of P-CPP suppressed total and specific IgE levels in the serum. Mice fed P-CPP exhibited low levels of OVA-specific IgG1 and increased OVA-specific IgG2a. P-CPP also suppressed IL-4 production, while D-CPP showed similar a level compared to that of the control. Further, P-CPP increased the population of the T follicular helper (Tfh) cell in the spleen. These results suggest that additional phosphorylation of CPP can enhance the attenuation of allergen-specific IgE-modulated allergic reactions in a murine food allergy model. [...]it is an important research subject to search and develop food dietary compounds that can safely and effectively suppress or inhibit the formation of antigen-specific IgE; prevent severe IgE-mediated, food-induced anaphylactic reactions; or promote oral immune tolerance [4]. Bovine milk protein is a major source of valuable bioactive peptides and is released upon enzymatic hydrolysis during gastrointestinal transit or upstream during food processing [5]. [...]Park and Nam suggested that most of the bioactivities of milk proteins are absent or incomplete in the original native protein, but full activities are observed upon proteolytic digestion, which releases and activates the bioactive peptides from the original protein [8]. Effects of Oral Administration of P-CPP and D-CPP against OVA-Induced IgE and Allergic Reactions All mice except naïve mice were sensitized twice by intraperitoneal immunization with 50 μg of OVA at an interval of 2 weeks prior to the oral challenge with 50 mg of food allergy model OVA and only PBS in the naïve group. |
| Author | Lebetwa, Ntshepisa Nakamura, Soichiro Tanaka, Sachi Suzuki, Yuta Katayama, Shigeru |
| AuthorAffiliation | 1 Interdisciplinary Graduate School of Science and Technology, Shinshu University, 8304 Minamiminowa, Ina, Nagano 399-4598, Japan; nlebetwa@gmail.com (N.L.); snakamu@shinshu-u.ac.jp (S.N.) 2 Department of Agricultural Research, Animal Production and Range research Division, Ministry of Agriculture, Private bag 0033, Gaborone BO320, Botswana 3 Faculty of Agriculture, Shinshu University, 8304 Minamiminowa, Ina, Nagano 399-4598, Japan; 18as207a@shinshu-u.ac.jp (Y.S.); tanakasa@shinshu-u.ac.jp (S.T.) |
| AuthorAffiliation_xml | – name: 1 Interdisciplinary Graduate School of Science and Technology, Shinshu University, 8304 Minamiminowa, Ina, Nagano 399-4598, Japan; nlebetwa@gmail.com (N.L.); snakamu@shinshu-u.ac.jp (S.N.) – name: 2 Department of Agricultural Research, Animal Production and Range research Division, Ministry of Agriculture, Private bag 0033, Gaborone BO320, Botswana – name: 3 Faculty of Agriculture, Shinshu University, 8304 Minamiminowa, Ina, Nagano 399-4598, Japan; 18as207a@shinshu-u.ac.jp (Y.S.); tanakasa@shinshu-u.ac.jp (S.T.) |
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| CitedBy_id | crossref_primary_10_1016_j_foodchem_2020_128656 crossref_primary_10_1021_acs_jafc_2c07326 crossref_primary_10_1590_1678_9199_jvatitd_2021_0047 crossref_primary_10_1038_s41598_022_08380_0 |
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| SubjectTerms | anti-allergic activity Antigens Body temperature Cytokines Food allergies Gene expression immunomodulation Milk Peptides phosphopeptide Phosphorylation Proteins Researchers |
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| Title | Enhanced Anti-Allergic Activity of Milk Casein Phosphopeptide by Additional Phosphorylation in Ovalbumin-Sensitized Mice |
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