title: Effects of 25-hydroxyvitamin D3 on cathelicidin production and antibacterial function of human oral keratinocytes.
abstract: Vitamin D and its metabolites have been recognized as key determinants in innate immune modulation. In this study, we investigated the regulation of antibacterial functions of oral keratinocyte cells by 25-hydroxyvitamin D3 (25VD3). OKF6/TERT2 cells, an immortalized human oral keratinocyte cell line, were transfected with or without 24-hydroxylase small interfering RNA (siRNA) and incubated with different amounts of 25VD3. These epithelial cells expressed high levels of inactivating 24-hydroxylase (CYP24A1) and relatively low levels of activating 1α-hydroxylase (CYP27B1) in the presence of 25VD3. 25VD3 influenced the expression of vitamin D-driven genes and cathelicidin in a dose-related manner. SiRNA specific to 24-hydroxylase augmented the cathelicidin production and subseqently influenced the antibacterial activity on multispecies of oral pathogens. These observations suggest that 25VD3 is capable of stimulating cathelicidin production and modulating antibacterial function upon CYP24A1 knochdown in oral epithelial cells, and indicate novel mechanisms that 25VD3 may enhance antibacterial ability in oral keratinocytes.
authors.affiliation: State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, 14 3rd Section S Renmin Road, Chengdu 610041, China. wqinno8751@gmail.com
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Wu
authors.initials: W
authors.lastname: Zhang
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Raydolf
authors.initials: R
authors.lastname: Aprecio
authors.forename: Wan
authors.initials: W
authors.lastname: Wu
authors.forename: Yiqiao
authors.initials: Y
authors.lastname: Lin
authors.forename: Yiming
authors.initials: Y
authors.lastname: Li
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis*; D015153:Blotting, Western; D002112:Calcifediol / Q000494:pharmacology*; D002460:Cell Line; D055785:Gene Knockdown Techniques; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D009061:Mouth Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D065668:Vitamin D3 24-Hydroxylase; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D034741:RNA, Small Interfering; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D002112:Calcifediol; D054804:Cathelicidins
keywords: 1α-Hydroxylase (CYP27B1); 24-Hydroxylase (CYP24A1); 25-Hydroxyvitamin D(3); Cathelicidin; Oral keratinocytes