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Nutritional Immunology

Retinoic Acid Decreases Adherence of Murine Myeloid Dendritic Cells and Increases Production of Matrix Metalloproteinase-9^1–3,

⁴ Department of Food Science and Human Nutrition and ⁵ Biomedical Laboratory Diagnostics Program, Michigan State University, East Lansing, MI 48824

^* To whom correspondence should be addressed: e-mail: hoagk{at}msu.edu.

Myeloid dendritic cells (DC) are professional antigen presenting cells (APC) that migrate to secondary lymphoid tissues upon antigen stimulation, where they activate naïve T cells. Vitamin A is essential for normal immune function. We investigated the ability of all-trans retinoic acid (atRA), a bioactive metabolite of vitamin A, to modulate DC adhesion in culture. Male BALB/cJ mouse bone marrow cells cultured with granulocyte-macrophage colony-stimulating factor in the presence of retinoic acid receptor (RAR) -specific antagonist showed an increase in the percentage of developing DC that remained adherent compared with cells rescued with atRA treatment from d 8 to 10 of culture (P < 0.05). Replacement of the RAR antagonist with atRA on d 8 of the culture period decreased DC surface expression of the adhesion molecule CD11a (P < 0.0001) but not the gene expression. Rescue with atRA also dramatically increased gene and protein expression of pro-matrix metalloproteinase (MMP)-9 (P < 0.05). However, gene expression and protein production of tissue inhibitor of metalloproteinase (TIMP)-1 was unaffected by atRA rescue, altering the molar ratio of secreted pro-MMP-9:TIMP-1, resulting in a fold excess of pro-MMP-9 to its primary inhibitor (P < 0.05). These data suggest that atRA is essential to augment MMP-9 expression in myeloid DC and can alter their surface expression of adhesion molecules.

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