title: Induction of triggering receptor expressed on myeloid cells (TREM-1) in airway epithelial cells by 1,25(OH)₂ vitamin D₃.
abstract: The airway epithelium plays a role in host defense through the binding of innate immune receptors, which leads to the activation of inflammatory mediators, including antimicrobial peptides. The active form of vitamin D, 1,25(OH)(2)D(3), induces the expression of the antimicrobial peptide LL-37 in both myeloid cells and airway epithelial cells (AEC). Here, we demonstrate that mRNA encoding triggering receptor expressed on myeloid cells (TREM)-1 was induced up to 12-fold by 1,25(OH)(2)D(3) in normal human bronchial epithelial (NHBE) cells and in well-differentiated cultures of six airway epithelial cell lines from patients with cystic fibrosis and healthy individuals. TREM-2 and DAP12 were also expressed in airway cultures, but not induced by vitamin D. Induction occurs through a vitamin D response element identified in its proximal promoter region, and was regulated by PU.1 expressed in the AEC. Activation of TREM-1 by a cross-linking antibody led to an induction of both human β-defensin-2 and TNF-α mRNA, demonstrating its functionality in these cells. Our results expand on the role played by the airway epithelium in innate immunity and suggest that vitamin D can modulate the innate immune defense of the airway epithelium, and could potentially be developed as an adjunctive therapy for airway infections.
authors.affiliation: Department of Oral Biology, UMDNJ-New Jersey Dental School, Newark, NJ, USA.
authors.forename: Isaura
authors.initials: I
authors.lastname: Rigo
authors.forename: Laura
authors.initials: L
authors.lastname: McMahon
authors.forename: Puneet
authors.initials: P
authors.lastname: Dhawan
authors.forename: Sylvia
authors.initials: S
authors.lastname: Christakos
authors.forename: Sunghan
authors.initials: S
authors.lastname: Yim
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Ryan
authors.forename: Gill
authors.initials: G
authors.lastname: Diamond
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D016133:Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D014162:Transfection; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D023083:beta-Defensins / Q000096:biosynthesis; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; C106641:DEFB4A protein, human; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins; D002117:Calcitriol; D054804:Cathelicidins