All‐trans retinoic acid up regulates matrix metalloproteinase‐9 activity by murine C57BL/6J myeloid dendritic cells

Abstract

Myeloid dendritic cells (DC) are specialized cells for antigen presentation. Upon activation in peripheral tissues, DC migrate to lymph nodes to present antigen to and activate T cells. Matrix metalloproteinase (MMP)‐9 is a gelatinase essential for DC migration to sites of infection and inflammation as well as to lymph nodes. We have previously shown that all‐trans retinoic acid (atRA), a bioactive metabolite of vitamin A, is important for release of DC from the surface of the tissue culture dish in vitro and that it significantly augments MMP‐9 mRNA and protein production. In the current studies, we investigated the effects of atRA on MMP‐9 activity related to DC adhesion in vitro. Mouse bone marrow cells cultured under myeloid DC generating conditions in the presence of a retinoic acid receptor antagonist demonstrated decreased gelatinase activity compared to cells rescued with atRA treatment for the last 48 hours of the culture period. DC cultured in the presence of atRA and a specific MMP‐9 inhibitor showed significant increase in the adherent cell yield and percentage of total cells and DC that are adherent in a dose dependent manner compared to cultures treated with atRA only for the full culture period. These data suggest that atRA regulates DC adhesion in vitro through MMP‐9 activity.Grant Funding SourceDepartment of Food Science and Human Nutrition, Michigan State University