IntroductionComplicated crosstalk between environmental factors and multiple genes determines which individuals will develop any given immune-mediated disease (Cantorna, 2010). Calcitriol [1α-25(OH)-vitamin D3] is one of the steroid hormone families and, similar to other members of these families, participates in the regulation of gene expression (Cantorna, 2010;Smyk et al., 2013). On the other hand, calcitriol may be an environmental factor that contributes to immune-mediated disease development. Environmental sources of calcitriol include diet and production in the skin following UV exposure to precursor 7-dehydrocholesterol (Namgung et al., 1994).Bone-marrow-derived mesenchymal stem cells (MSCs) are multipotent and can give rise to mesenchymal tissues like bone, cartilage, and fat (Uccelli et al., 2008). They also have potent immunomodulatory properties and may be valuable tools for cell-based immunotherapy (Meirelles Lda et al., 2009;Ghannam et al., 2010;Zhang et al., 2013). MSCs in bone marrow and tissue form a niche that has inevitable interactions with hematopoietic cells including neutrophils (Raffaghello et al., 2008;Maqbool et al., 2011). Neutrophils are one of the major cell types that constitute innate immunity. They predominate in host tissues during acute inflammatory processes (Greenberg and Grinstein, 2002).Recent documents have shown that calcitriol has an important role in regulating the growth of MSCs (Artaza et al., 2010;Klotz et al., 2012). The present study was carried out to investigate the effects of calcitriol on the interaction between bone-marrow-derived MSCs and neutrophils in rats. Materials and methods MaterialsPropidium iodide, acridine orange, and phosphatebuffered saline (PBS) were procured from Sigma-Aldrich (St Louis, MO, USA). May-Grünwald-Giemsa stain was purchased from Merck (Darmstadt, Germany) and dextran was obtained from Fresenius Kabi (Verona, Italy). Fetal calf serum, Dulbecco's Modified Eagle Medium (DEMEM), and RPMI 1640 were purchased from GIBCO/Life Technologies Inc. (Gaithersburg, MD, USA). The enzymelinked immunosorbent assay (ELISA) kit for interleukin (IL)-6 was purchased from Bender MedSystems

The educated monocytes with MCM may be as a promising strategy for cell-based therapies of asthma.

This study was conducted to investigate the effects of the oestradiol (ES)pulsed bone marrow-derived mesenchymal stem cell (BM-MSC) to treat adjuvant-induced arthritis in Wistar rats. BM-MSCs were pulsed with ES (0, 10,100 and 1000 nM) for 24 hours. RA induced collagen and Freund's Complete Adjuvant into the base of the tail of Wistar rats. In vitro results showed that the least effective concentration of ES that can promote potent anti-inflammatory properties in the MSC population is 100 nM. At this concentration, ES increases the inhibition of the poly-clonal T lymphocyte proliferation, production of IDO, IL-10, Nitric oxide, TGF-β, and expression of CXCR4 and CCR2 mRNA in the MSC population. Based on In vitro results, the RA rats were treated with 2×106 MSCs or ES-pulsed MSCs (100nM) on day 10 when all animals had developed signs of RA. The in vivo results showed that the treatment with ES-pulsed BM-MSCs reduced the severity of the RA more profoundly than treatment with BM-MScs alone. The ability of ES-pulsed BM-MSCs to reduce symptoms and RA markers like CRP, RF, and nitric oxide was comparable to that of prednisolone. Prednisolone was more successful in reducing inflammatory cytokines than treatment with ES-pulsed BM-MSCs. ES-pulsed BM-MSCs were more successful in increasing anti-inflammatory cytokines than treatment with Prednisolone. The ability of ES-pulsed BM-MSCs to decrease the level of nitric oxide was comparable to that of prednisolone. Collectively, ES-pulsed BM-MSCs may be a helpful strategy in controlling RA.

Background: Recent documents indicate that mesenchymal stem cells (MSCs) express vitamin D3 receptors and communicate with other immunocytes. However, there is no information about the role of vitamin D3 on the crosstalk between MSCs and macrophages. Objectives: The present study was done to investigate the effects of the MSCs treated with 1α-25(OH)-vitamin D3 on the some of the macrophages functions. Methods: In this experimental study, mesenchymal stem cells were isolated from bone marrow of Wistar male rats (8-10 weeks old) and pulsed with different concentration of vitamin D3 (0, 50, 100 and 200 nM) for 48 hours. After 24 hours, the supernatants of MSCs were collected and incubated overnight with macrophages. Next, vitality, neutral red uptake, phagocytic activity, respiratory burst, and killing activity of macrophages were evaluated. Data were analyzed using the one-way ANOVA through SPSS software version 20. Results: The supernatants of MSCs treated with vitamin D3 could significantly enhance the macrophage vitality and uptake of neutral red as well as phagocytic activity of macrophages. Supernatants of MSCs pulsed with vitamin D3 reduced tetradecanoylphorbol acetate induced respiratory burst of macrophages more profoundly than the supernatants of MSCs alone. Nevertheless, the killing activity of macrophages triggered by opsonized yeast didn't show any significant effect by supernatants of MSCs pulsed with vitamin D3 compared to the supernatants of MSCs alone. Conclusions: The supernatants of vitamin D3 treated MSCs potentiate the anti-inflammatory functions of MSCs-educated macrophages without any change in microbicidal potential of macrophages after challenge with opsonized pathogen cannot be altered.