Anti‑inflammatory effect of 1,25‑dihydroxyvitamin D3 is associated with crosstalk between signal transducer and activator of transcription 5 and the vitamin D receptor in human monocytes

Yang,Mengxue; Yang,Bo; Gan,Hua; Li,Xianwen; Xu,Jie; Yu,Jie; Gao,Lin; Li,Fengping

doi:10.3892/etm.2015.2321

Anti‑inflammatory effect of 1,25‑dihydroxyvitamin D3 is associated with crosstalk between signal transducer and activator of transcription 5 and the vitamin D receptor in human monocytes

Authors:
- Mengxue Yang
- Bo Yang
- Hua Gan
- Xianwen Li
- Jie Xu
- Jie Yu
- Lin Gao
- Fengping Li
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Affiliations: Department of Endocrinology, First Afﬁliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China, Department of Nephrology, First Afﬁliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, School of Public Health, Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China
Published online on: March 2, 2015 https://doi.org/10.3892/etm.2015.2321
Pages: 1739-1744

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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)2D3 and 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)2D3 group 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)2D3 may be associated with crosstalk between STAT5 and VDR, which further induces cytoskeletal rearrangement.

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