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Plasma folate levels are inversely associated with natural killer cell degranulation in mice (135.1)
Author(s) -
Warzyszynska Joanna,
Sohn KyoungJin,
Spring Christopher,
Duan Angela,
Kim SungEun,
Carlyle James,
Kim YoungIn
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.135.1
Subject(s) - ionomycin , degranulation , endocrinology , medicine , stimulation , natural killer cell , cytokine , flow cytometry , phorbol , biology , immunology , chemistry , cytotoxicity , biochemistry , in vitro , receptor , signal transduction , protein kinase c
High intake and plasma levels of folic acid (FA), the synthetic form of the B‐vitamin folate, were associated with reduced natural killer (NK) cell cytotoxicity in post‐menopausal women. This observation has not yet been confirmed. Thus, we examined the relationship between dietary FA intake/plasma folate levels and NK cell activity in an animal model. Post‐weaning C57BL/6 mice were randomized to receive diets containing 2 (control) or 20 mg FA/kg diet for 3 months. A flow cytometry based CD107a and IFN‐γ detection assay was used to assess splenic NK cell activity. Plasma folate levels were significantly higher ( p < 0.0001) in the high FA group. Plasma folate levels were significantly and inversely associated with the frequency of NK cell degranulation (%CD107a+ NK cells) in response to stimulation with the mouse T‐cell lymphoma YAC‐1 and cytokines ( r s = ‐0.520; p = 0.035) but not in response to mitogenic stimulation with phorbol 12‐myristate 13‐acetate (PMA) and ionomycin. Plasma folate levels were not associated with IFN‐γ production (%IFN‐γ+ NK cells) in response to either YAC‐1 and cytokine or PMA/ionomycin stimulation. Our findings corroborate an inverse association between high FA levels and NK cell cytotoxicity and suggest that reduced target cell recognition, evidenced by reduced degranulation in response to cancer cell targets but not in response to mitogenic stimulation, is a likely mechanism behind this inverse association. Our data suggest that impaired NK cell function may be a mechanism behind the purported tumor‐promoting effect associated with high FA supplementation. Grant Funding Source : Supported by CIHR MOP #14126