Calcitriol modulates the effects of the supernatants of bone-marrow–derived mesenchymal stem cells on neutrophil functions

Abstract

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

Caffeine alters the effects of bone marrow-derived mesenchymal stem cells on neutrophils

“…25,29 The MTT assay is a rapid test for assessing cell viability. 11 The findings showed that caffeine at higher doses could significantly decrease the protective role of MSCs on neutrophils apoptosis. Previous studies indicated that MSCs diminish the mitochondrial pro-apoptotic protein, Bax in neutrophils through IL-6 secretion.…”

“…5,6 Neutrophils are the most prominent cell type of the innate immune system and are predominant in host tissues during acute inflammatory processes. 11,24 Neutrophils may also play an effective role in adaptive immunity. 24 Mature neutrophils are normally found in the bloodstream and inflamed tissues, instead of bone marrow.…”

“…Similar to the present study, some former studies also used the bone marrow derived MSCs to investigate the interaction between MSCs and neutrophils. 11,27 Neutrophil homeostasis and turnover are highly regulated in the body. Circulating neutrophils have a short life span of 6-10 h, after which the cells undergo apoptosis.…”

“…The neutrophils were washed and suspended in DMEM. 11 Following this procedure, the purity of neutrophils was 95%.…”

“…[8][9][10] It has been observed that the MSCs' functions are under the control of a large number of signaling systems. [11][12][13] Interestingly, it has been shown that MSCs express all four adenosine receptors' subtypes, and stimulation of these receptors plays an active role in bone marrow-derived mesenchymal stem cell proliferation and differentiation. 14 The interaction between MSCs and immunocytes, such as neutrophils, has been investigated in some recent studies.…”