title: Anti-inflammatory effect of 1,25-dihydroxyvitamin D3is associated with crosstalk between signal transducer and activator of transcription 5 and the vitamin D receptor in human monocytes.
abstract: 1,25-Dihydroxyvitamin D3(1,25-(OH)2D3) has an anti-inflammatory effect on human monocytes incubated with sera from patients with type 2 diabetes/diabetic nephropathy; however, the detailed mechanism behind the effect remains to be explored. The current study further validated the effects of 1,25-(OH)2D3and lipopolysaccharide (LPS) + human recombinant interleukin (IL)-15 on the expression of the vitamin D receptor (VDR) and phosphorylated signal transducer and activator of transcription 5 (p-STAT5) in human monocytes and explored the possible interaction between VDR and p-STAT5. Synchronized THP-1 cells were divided into pre-intervened groups, namely the control, LPS + IL-15 and 1,25-(OH)2D3, groups, according to their differing treatments. The expression of STAT5 and p-STAT5 was evaluated by western blot analysis; the concentration of IL-6 in the supernatant was determined using an enzyme-linked immunosorbent assay; the expression of cytoskeletal proteins was observed using immunofluorescence and laser confocal microscopy; and the possible intranuclear interaction between VDR and p-STAT5 was investigated using immunofluorescence, immuno-coprecipitation and western blot analysis. LPS + IL-15 upregulated p-STAT5 expression and the IL-6 level (P<0.05), with cytoskeletal rearrangement. These effects were partially prevented through pretreatment with 1,25-(OH)2D3. The LPS + IL-15 group and the 1,25-(OH)2D3group exhibited an interaction between p-STAT5 and VDR in the nucleus, with the latter group showing a significant increase compared with the former (P<0.05). The immuno-coprecipitation results provided evidence of the interaction between VDR and p-STAT5, which suggests the existence of STAT5-VDR crosstalk in THP-1 monocytes. Cytoskeletal rearrangement, VDR and p-STAT5 potentially have interactions in THP-1 monocytes. The anti-inflammatory effect of 1,25-(OH)2D3may be associated with crosstalk between STAT5 and VDR, which further induces cytoskeletal rearrangement.
authors.affiliation: Department of Endocrinology, First Afﬁliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
authors.forename: Mengxue
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, First Afﬁliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
authors.forename: B O
authors.initials: BO
authors.lastname: Yang
authors.affiliation: Department of Nephrology, First Afﬁliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Gan
authors.affiliation: Department of Endocrinology, First Afﬁliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
authors.forename: Xianwen
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Public Health, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: School of Public Health, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Endocrinology, First Afﬁliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Gao
authors.affiliation: Department of Endocrinology, First Afﬁliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
authors.forename: Fengping
authors.initials: F
authors.lastname: Li
keywords: 1,25-dihydroxyvitamin D3; interleukin-15; lipopolysaccharide; monocyte; signal transducer and transcription activator; vitamin D receptor