title: Upregulation of interleukin-1β production by 1,25-dihydroxyvitamin D(3) in activated human macrophages.
abstract: 1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) plays important roles in the immune system. In contrast to its well known function in the adaptive immune system, much less is known about the immunoregulatory effects of 1,25(OH)(2)D(3) in the innate immune system, especially on activated human macrophages. Here we found that 1,25(OH)(2)D(3) strongly stimulated the production of interleukin-1β (IL-1β) in PMA-differentiated U937 cells and human monocyte-derived macrophages treated with lipopolysaccharide (LPS) or PMA. In this study, Erk1/2 appeared to mediate 1,25(OH)(2)D(3)-induced expression of IL-1β. Parallel to the increased production of IL-1β, 1,25(OH)(2)D(3) increased the expression and phosphorylation of the CCAAT enhancer-binding protein β (C/EBPβ), which is one of the key transcriptional regulatory factors for IL-1β transcription. These results suggest that 1,25(OH)(2)D(3) may function as a proinflammatory molecule in inflammatory macrophages.
authors.affiliation: The Hospital for Rheumatic Diseases, Hanyang University, Seoul, Korea.
authors.forename: Bit-Na-Ra
authors.initials: BN
authors.lastname: Lee
authors.forename: Tae-Hwan
authors.initials: TH
authors.lastname: Kim
authors.forename: Jae-Bum
authors.initials: JB
authors.lastname: Jun
authors.forename: Dae-Hyun
authors.initials: DH
authors.lastname: Yoo
authors.forename: Jin-Hyun
authors.initials: JH
authors.lastname: Woo
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Choi
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Lee
authors.forename: Gwan Gyu
authors.initials: GG
authors.lastname: Song
authors.forename: Yongjin
authors.initials: Y
authors.lastname: Kim
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Jeongwon
authors.initials: J
authors.lastname: Sohn
authors.forename: Jong Dae
authors.initials: JD
authors.lastname: Ji
mesh_terms: D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000235:genetics; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology; D010766:Phosphorylation / Q000187:drug effects; D020871:RNA Stability / Q000187:drug effects; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D020298:U937 Cells; D015854:Up-Regulation / Q000187:drug effects*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D053583:Interleukin-1beta; C118756:dihydroxy-vitamin D3; D014807:Vitamin D; D048049:Extracellular Signal-Regulated MAP Kinases