Vitamin A Upregulates Matrix Metalloproteinase-9 Activity by Murine Myeloid Dendritic Cells through a Nonclassical Transcriptional Mechanism
| Autor: | Denise E. Lackey, Kathleen A. Hoag |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
Transcription Genetic Receptors Retinoic Acid Retinoic acid Medicine (miscellaneous) Tretinoin Matrix Metalloproteinase Inhibitors Biology Histones Mice Histone H3 chemistry.chemical_compound Cell Adhesion medicine Animals Gelatinase p300-CBP Transcription Factors RNA Messenger Enzyme Inhibitors Promoter Regions Genetic Vitamin A Histone H3 acetylation Cells Cultured Nutrition and Dietetics Retinoic Acid Receptor alpha Nuclear Proteins Acetylation DNA Dendritic Cells Up-Regulation Cell biology Mice Inbred C57BL Retinoic acid receptor Matrix Metalloproteinase 9 Biochemistry chemistry Retinoic acid receptor alpha Chromatin immunoprecipitation medicine.drug |
| Zdroj: | The Journal of Nutrition. 140:1502-1508 |
| ISSN: | 0022-3166 |
| DOI: | 10.3945/jn.110.122556 |
| Popis: | Myeloid dendritic cells (DC) are specialized antigen-presenting immune cells. Upon activation in peripheral tissues, DC migrate to lymph nodes to activate T lymphocytes. Matrix metalloproteinase (MMP)-9 is a gelatinase essential for DC migration. We have previously shown that all-trans retinoic acid (atRA), a bioactive metabolite of vitamin A, significantly augmented DC MMP-9 mRNA and protein production. We investigated the mechanisms by which atRA increased MMP-9 activity in vitro. Mouse myeloid DC cultured with atRA demonstrated increased gelatinase activity compared with cells cultured with retinoic acid receptor (RAR)-alpha antagonist. Adding MMP-9 inhibitor significantly blocked DC gelatinase activity and increased adherence of DC in a dose-dependent manner. AtRA-induced Mmp-9 gene expression in DC was blocked by transcriptional inhibition. Because the Mmp-9 promoter contains no canonical retinoic acid response element (RARE), we performed additional studies to determine how atRA regulated DC Mmp-9 transcription. Electrophoretic mobility shift assays for the consensus Sp1, activating protein-1, and nuclear factor-kappaB binding sites located in the Mmp-9 promoter did not indicate greater nuclear protein binding in response to atRA. Chromatin immunoprecipitation assays indicated RARalpha and histone acetyltransferase p300 recruitment to, and acetylation of, histone H3 at the Mmp-9 promoter was greater after atRA treatment. These data suggest that atRA regulated DC adhesion in vitro partly through MMP-9 gelatinase activity. Mmp-9 expression was enhanced through a transcriptional mechanism involving greater RARalpha promoter binding, recruitment of p300, and subsequent histone H3 acetylation, despite the absence of a consensus RARE. |
| Databáze: | OpenAIRE |
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