title: Effects of all-trans retinoic acid, retinol, and β-carotene on murine macrophage activity.
abstract: Previous studies have demonstrated that vitamin A and carotenoids regulate immune function in lymphocytes and splenocytes, and that the carotenoid lutein regulates matrix metalloproteinase-9 (MMP-9) production in macrophages. In this study, we investigated the effects of all-trans retinoic acid (atRA, a bioactive vitamin A metabolite), retinol (vitamin A), and β-carotene (vitamin A precursor) on the activity of murine RAW264.7 and peritoneal macrophages. Our results indicated that atRA and retinol could induce GM-CSF and IL-16 expression, whereas all these tested substances enhanced MMP-9 production. Interestingly, the expression of GM-CSF, IL-16, and MMP-9 was distinctly regulated by these three substances. AtRA and retinol affected GM-CSF and IL-16 expression mainly through RA receptor β (RARβ). However, atRA induced MMP-9 production was via RARα activation and retinol and β-carotene caused MMP-9 production via RARα and β activation. These were supported by the observations that the RARα and β agonists/antagonists differentially affected MMP-9 production and that atRA and β-carotene enhanced RARE-mediated and MMP-9 promoter luciferase activity. In parallel, while the MMP-9 induction by atRA was not affected by the MAPKs inhibitors, its induction by retinol and β-carotene was repressed by the inhibitor targeting ERK1/2. Finally, we show that all the tested substances could functionally enhance macrophage phagocytosis. Taken together, we provide evidence here for the first time that atRA, retinol, and β-carotene differentially regulate GM-CSF, IL-16, and MMP-9 production in macrophages, explaining at least in part why these vitamin A-related substances are beneficial for immunity.
authors: School of Medicine, Fu-Jen Catholic University, Wen-Bin Wu, No.510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City 24205, Taiwan. wenbin@mail.fju.edu.tw.
authors: Huey-Ming
authors: HM
authors: Lo
authors: Shih-Wei
authors: SW
authors: Wang
authors: Chih-Li
authors: CL
authors: Chen
authors: Pi-Hui
authors: PH
authors: Wu
authors: Wen-Bin
authors: WB
authors: Wu
mesh_terms: D000818:Animals; D002460:Cell Line; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology*; D020780:Matrix Metalloproteinase 9 / Q000276:immunology; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects; D018168:Receptors, Retinoic Acid / Q000276:immunology; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin / Q000494:pharmacology*; D014801:Vitamin A / Q000494:pharmacology*; D019207:beta Carotene / Q000494:pharmacology*
chemical_list: C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D019207:beta Carotene; D014801:Vitamin A; D014212:Tretinoin; D020780:Matrix Metalloproteinase 9