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Deventer, Netherlands

Willems H.M.E.,VU University Amsterdam | Van Den Heuvel E.G.H.M.,Royal FrieslandCampina Research | Carmeliet G.,Catholic University of Leuven | Schaafsma A.,Innovation International | And 2 more authors.
Steroids | Year: 2012

1,25-Dihydroxyvitamin D 3 (1,25(OH) 2D 3) strongly mediates bone mass. Mechanical stimulation also affects bone mass, partly via enhancing nitric oxide (NO) production by osteoblasts. We aimed to determine whether 1,25(OH) 2D 3 affects NO production by osteoblasts in the presence or absence of mechanical stimulation. We hypothesised that 1,25(OH) 2D 3 stimulates NO production via nuclear actions of the vitamin D receptor (VDR), which requires hours of incubation with 1,25(OH) 2D 3 to occur. MC3T3-E1 osteoblasts and long-bone osteoblasts of adult wildtype and VDR -/- mice were pre-incubated for 24 h with or without 1,25(OH) 2D 3 (10 -13-10 -9 M), followed by 30 min pulsating fluid flow (PFF; 0.7 ± 0.3 Pa, 5 Hz) or static culture with or without 1,25(OH) 2D 3. NO production and NO synthase (NOS) expression were quantified. 10 -11 M 1,25(OH) 2D 3 for 24 h, but not 30 min, stimulated NO production by MC3T3-E1 osteoblasts (eightfold). 1,25(OH) 2D 3 for 24 h increased inducible-NOS gene-expression (twofold), suggesting that 1,25(OH) 2D 3 stimulated NO production via activation of NOS gene transcription. PFF rapidly increased NO production by MC3T3-E1 osteoblasts, wildtype osteoblasts, and VDR -/- osteoblasts. This PFF effect was abolished after incubation with 1,25(OH) 2D 3 for 24 h, or during PFF only. Our results suggest that 1,25(OH) 2D 3 stimulates inducible-NOS expression and NO production by osteoblasts in the absence of mechanical stimulation, likely via genomic VDR action. In contrast, 1,25(OH) 2D 3 may affect mechanical loading-induced NO production independent of genomic VDR action, since 1,25(OH) 2D 3 diminished PFF-induced NO production in VDR -/- bone cells. In conclusion, 1,25(OH) 2D 3 and mechanical loading interact at the level of mechanotransduction, whereby 1,25(OH) 2D 3 seems to act independently of VDR genomic mechanism. © 2011 Elsevier Inc. All rights reserved. Source

den Hartog G.,Wageningen University | Savelkoul H.F.J.,Wageningen University | Schoemaker R.,Royal FrieslandCampina Research | Tijhaar E.,Wageningen University | And 4 more authors.
PLoS ONE | Year: 2011

Cytokines can be functionally active across species barriers. Bovine IL-10 has an amino acid sequence identity with human IL-10 of 76.8%. Therefore, the aim of this study was to evaluate whether bovine IL-10 has immunomodulatory activities on human monocytes and dendritic cells. Peripheral blood monocytes were isolated from healthy donors, and used directly or allowed to differentiate to dendritic cells under the influence of IL-4 and GM-CSF. Recombinant bovine IL-10 inhibited TLR induced activation of monocytes, and dose-dependently inhibited LPS-induced activation of monocyte-derived DCs comparable to human IL-10. By using blocking antibodies to either bovine IL-10 or the human IL-10 receptor it was demonstrated that inhibition of monocyte activation by bovine IL-10 was dependent on binding of bovine IL-10 to the human IL-10R. These data demonstrate that bovine IL-10 potently inhibits the activation of human myeloid cells in response to TLR activation. Bovine IL-10 present in dairy products may thus potentially contribute to the prevention of necrotizing enterocolitis and allergy, enhance mucosal tolerance induction and decrease intestinal inflammation and may therefore be applicable in infant foods and in immunomodulatory diets. © 2011 den Hartog et al. Source

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