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      Vitamin C Up-regulates Expression of CD80, CD86 and MHC Class II on Dendritic Cell Line, DC-1 Via the Activation of p38 MAPK

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          Abstract

          Vitamin C is an essential water-soluble nutrient which primarily exerts its effect on host defense mechanisms and immune homeostasis, but the mechanism related to immune-potentiation is poorly understood. Since dendritic cells (DCs) are known as a potent antigen presenting cell (APC) that could enhance the antigen specific immune responses, we investigate the effects of vitamin C on activation of DCs and its related mechanism by using dendritic cell lines, DC-1. First, we found that there was no damage on DC-1 by 2.5 mM of vitamin C. In the presence of vitamin C, the expression of CD80, CD86, and MHC molecules was increased, but it was decreased by the pre-treatment of SB203580, p38 MAPK-specific inhibitor. We confirmed the phosphorylation of p38 MAPK was increased by the treatment of vitamin C. Taken together, these results suggest that vitamin C could enhance the activity of dendritic cells via the up-regulation of the expression of CD80, CD86, and MHC molecules and the activation of p38 MAPK is related to this process.

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          Most cited references28

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          Effects of vitamin C on intracytoplasmic cytokine production in human whole blood monocytes and lymphocytes.

          Vitamin C (ascorbic acid) is an essential water-soluble nutrient which primarily exerts its effect on immune homeostasis as physiological antioxidant. However, conflicting data exist regarding the effect of vitamin C on the expression of pro-inflammatory cytokines. It was the aim of this study to investigate the impact of vitamin C on intracytoplasmic production of pro-inflammatory cytokines in monocytes and lymphocytes by flow cytometry after human whole blood assay. Vitamin C dose dependently inhibited the LPS-induced number of monocytes producing IL-6 (e.g., 41.0% reduction, p < 0.001, 20 mM vitamin C) and TNF-alpha (e.g., 26.0% reduction, p < 0.005, 20 mM vitamin C). Simultaneously, the number of lymphocytes producing IL-2 after PMA/ionomycin stimulation was dose dependently reduced (e.g., 24.2% inhibition, p < 0.005, 20 mM vitamin C). Notably, the number of IL-1 and IL-8 producing monocytes as well as TNF-alpha and IFN-gamma producing lymphocytes were not significantly affected by 20 mM vitamin C. These data suggest that vitamin C selectively influences intracytoplasmic cytokine production and therefore, further studies are needed to elucidate the underlying mechanisms of immunomodulation, i.e. regulation of NF kappa B activation which is mandatory for the induction of pro-inflammatory cytokines.
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            Cloning and functional characterization of the human sodium-dependent vitamin C transporters hSVCT1 and hSVCT2.

            Two sodium-dependent vitamin C transporters, hSVCT1 and hSVCT2, were cloned from a human kidney cDNA library. hSVCT1 had a 1797 bp open reading frame encoding a 598 amino acid polypeptide. The 1953 bp open reading frame of hSVCT2 encoded a 650 amino acid polypeptide. Using a Xenopus laevis oocyte expression system, both transporters were functionally expressed. By Eadie-Hofstee transformation the apparent K(m) of hSVCT1 for ascorbate was 252.0 microM and of hSVCT2 for ascorbate was 21.3 microM. Both transporters were sodium-dependent and did not transport dehydroascorbic acid. Incubation of oocytes expressing either transporter with phorbol 12-myristate 13-acetate (PMA) inhibited ascorbate transport activity. Availability of the human transporter clones may facilitate new strategies for determining vitamin C intake.
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              Enhancement of natural killer cell activity and T and B cell function by buffered vitamin C in patients exposed to toxic chemicals: the role of protein kinase-C.

              After exposure to many toxic chemicals, NK function can be decreased significantly. Weeks or months later, natural killer (NK) function can rebound to normal levels in some and can be suppressed for prolonged periods of time in other patients. In view of this, we decided to study the effect of buffered vitamin C on NK, T and B cell function in patients who had been exposed to toxic chemicals. After the first blood draw, 55 patients immediately ingested granulated buffered vitamin C in water at a dosage of 60 mg/Kg body weight. Exactly 24 hours later, blood was again drawn for a follow-up study of NK, T and B cell function. Vitamin C in high oral dose was capable of enhancing NK activity up to ten-fold in 78% of patients. Lymphocyte blastogenic responses to T and B cell mitogens were restored to the normal level after vitamin C usage. Signal transduction enzyme protein kinase C (PKC) appeared to be involved in the mechanism of induction of NK activity by vitamin C. We conclude that immune functional abnormalities can be restored after toxic chemical exposure by oral usage of vitamin C.
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                Author and article information

                Journal
                Immune Netw
                Immune Netw
                IN
                Immune Network
                The Korean Association of Immunologists
                1598-2629
                2092-6685
                December 2012
                31 December 2012
                : 12
                : 6
                : 277-283
                Affiliations
                [1 ]School of Korean Medicine, Pusan National University, Pusan 626-870, Korea.
                [2 ]Laboratory of Immunology and Vitamin C, Department of Anatomy, Seoul National University College of Medicine, Seoul 110-799, Korea.
                Author notes
                Corresponding Author. Jae Seung Kang, Laboratory of Immunology and Vitamin C, Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea. Tel: 82-2-740-8132; Fax: 82-2-741-8202; genius29@ 123456snu.ac.kr , Wang Jae Lee, Laboratory of Immunology and Vitamin C, Department of Anatomy, Seoul National University College of Medicine, Seoul, Korea. Tel: 82-2-740-8208; Fax: 82-2-745-9528; kinglee@ 123456snu.ac.kr
                Article
                10.4110/in.2012.12.6.277
                3566423
                23396903
                dbd5945e-0873-4d9c-b2b7-fadb40617c2a
                Copyright © 2012 The Korean Association of Immunologists

                This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 November 2012
                : 11 December 2012
                : 14 December 2012
                Categories
                Original Article

                Immunology
                vitamin c,dendritic cell,cd80,cd86,mhc class ii,p38 mapk
                Immunology
                vitamin c, dendritic cell, cd80, cd86, mhc class ii, p38 mapk

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