title: 25(OH) vitamin D suppresses macrophage adhesion and migration by downregulation of ER stress and scavenger receptor A1 in type 2 diabetes.
abstract: Cardiovascular disease (CVD) is the leading cause of mortality in patients with type 2 diabetes mellitus (T2DM). Vitamin D deficiency is not only more prevalent in diabetics but also doubles the risk of developing CVD. However, it is unknown whether 25-hydroxy vitamin D [25(OH)D3] replacement slows monocyte adhesion and migration, critical mechanisms involved in atherosclerosis progression. In this study, monocytes from vitamin D-deficient diabetic patients were cultured either in the patient's serum or in vitamin D-deficient media with or without 25(OH)D3 treatment. Adding 25(OH)D3 to monocytes cultured in vitamin D-deficient serum or media decreased monocyte adhesion to fibronectin and migration stimulated by monocyte chemotactic protein 1 (MCP-1). Accordingly, 25(OH)D3 decreased adhesion marker β1- and β2-integrin expression and migration receptor chemokine (C-C motif) receptor 2 (CCR2) expression. 25(OH)D3 treatment downregulated monocyte endoplasmic reticulum (ER) stress and scavenger receptor class A, type 1 (SR-A1) expression. The absence of SR-A1 prevented the increased macrophage adhesion and migration induced by vitamin D deficiency. Moreover, the absence of SR-A1 prevented the induction of adhesion and migration and expression of their associated membrane receptors by Thapsigargin, an ER stress inducer. These results identify cellular activation of monocyte/macrophage vitamin D signaling through 25(OH)D3 as a potential mechanism that could modulate adhesion and migration in diabetic subjects. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.
authors.affiliation: Division of Endocrinology, Metabolism, and Lipid Research, Washington University, 660 South Euclid Avenue, Campus Box 8127, St. Louis, MO 63110, USA. Electronic address: ariek@dom.wustl.edu.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Riek
authors.affiliation: Division of Endocrinology, Metabolism, and Lipid Research, Washington University, 660 South Euclid Avenue, Campus Box 8127, St. Louis, MO 63110, USA. Electronic address: joh@dom.wustl.edu.
authors.forename: Jisu
authors.initials: J
authors.lastname: Oh
authors.affiliation: Division of Endocrinology, Metabolism, and Lipid Research, Washington University, 660 South Euclid Avenue, Campus Box 8127, St. Louis, MO 63110, USA. Electronic address: idarwech@dom.wustl.edu.
authors.forename: Isra
authors.initials: I
authors.lastname: Darwech
authors.affiliation: Division of Endocrinology, Metabolism, and Lipid Research, Washington University, 660 South Euclid Avenue, Campus Box 8127, St. Louis, MO 63110, USA.
authors.forename: Clare E
authors.initials: CE
authors.lastname: Moynihan
authors.affiliation: Division of Endocrinology, Metabolism, and Lipid Research, Washington University, 660 South Euclid Avenue, Campus Box 8127, St. Louis, MO 63110, USA.
authors.forename: Robin R
authors.initials: RR
authors.lastname: Bruchas
authors.affiliation: Division of Endocrinology, Metabolism, and Lipid Research and Department of Cell Biology and Physiology, Washington University, 660 South Euclid Avenue, Campus Box 8127, St. Louis, MO 63110, USA. Electronic address: cbernal@dom.wustl.edu.
authors.forename: Carlos
authors.initials: C
authors.lastname: Bernal-Mizrachi
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D015536:Down-Regulation; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000473:pathology; D051117:Scavenger Receptors, Class A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D051117:Scavenger Receptors, Class A; D014807:Vitamin D; C104450:25-hydroxyvitamin D
keywords: Adhesion; Diabetes; Macrophage; Migration; SR-A1; Vitamin D