title: The effects of vitamin A on cells of innate immunity in vitro.
abstract: Retinoid treatment is suggested to promote development of inflammatory bowel disease, although preclinical studies are not supportive. We evaluated the effect of retinoids on cytokine response in in vitro-differentiated human dendritic cells (ivDCs) and macrophages (ivMACs) derived from healthy human donors and in cultured human THP-1 cells. Effect on human intestinal epithelial cell integrity was also assessed. Each cell type was incubated (±lipopolysaccharide [LPS]) with all-trans retinoic acid (ATRA), 13-cis-RA (isotretinoin) and 4-oxo-13-cis-RA. Cytokine analysis was performed by array analysis. Cultured human endothelial colorectal adenocarcinoma (Caco-2) cells were incubated with these retinoids and media analyzed for leakage by spectrofluorometric analysis. ATRA consistently and significantly inhibited LPS-induced release of the pro-inflammatory cytokines tumor necrosis factor, interleukin (IL)-6, macrophage inflammatory protein (MIP)-1α and MIP-1β. All retinoids tested stimulated release of the anti-inflammatory cytokines granulocyte-macrophage colony-stimulating factor and IL-10, and also monocyte chemotactic protein-1, vascular endothelial growth factor and eotaxin-1. Incubation with retinoids did not significantly alter the permeability of Caco-2 monolayers. Pre-treatment of each cell type with retinoids promoted an anti-inflammatory cytokine profile with only minimal effect on intestinal epithelial cell permeability; consistent with in vivo studies.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, University-Hospital of Zürich, Switzerland.
authors.forename: Kacper A
authors.initials: KA
authors.lastname: Wojtal
authors.forename: Lutz
authors.initials: L
authors.lastname: Wolfram
authors.forename: Isabelle
authors.initials: I
authors.lastname: Frey-Wagner
authors.forename: Silvia
authors.initials: S
authors.lastname: Lang
authors.forename: Michael
authors.initials: M
authors.lastname: Scharl
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Vavricka
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
mesh_terms: D000328:Adult; D018938:Caco-2 Cells; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010539:Permeability; D012176:Retinoids / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D012176:Retinoids