Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using mouse peritoneal mast cells, we investigated the effects of 1 alpha,25-dihydroxyvitamin D3 (calcitriol) on mast cell proliferation and histamine release. Calcitriol did not affect IL-3/IL-4-dependent mast cell proliferation, but it selectively inhibited stem cell factor-dependent mast cell proliferation and colony formation. Immunohistochemical and immunoblot analyses revealed that calcitriol treatment reduced expression of purified peritoneal mast cell c-kit protein. Using a mast cell line, MC/9, both c-kit protein and c-kit mRNA transcript were seen to be reduced following calcitriol treatment. Calcitriol also reduced histamine release induced by calcium ionophore A23187. In contrast, anti-IgE antibody-dependent histamine release was not affected by calcitriol. Our results indicate that calcitriol inhibits mast cell proliferation and A23187-induced histamine release that might be associated with a decreased expression of c-kit receptor.
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PMID:Inhibitory effect of 1 alpha,25-dihydroxyvitamin D3 on mast cell proliferation and A23187-induced histamine release, also accompanied by a decreased c-kit receptor. 893 75

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] is a secosteroid hormone that regulates bone metabolism, controls calcium homeostasis, and possesses immunomodulatory properties. We show here that 1,25(OH)2D3 contributes to the regulation of development and function of mast cells, which play a critical role in several inflammatory disorders. 1,25(OH)2D3 promotes apoptosis and inhibits maturation of mouse bone marrow-derived mast cell precursors. Dose-dependent inhibition of mast cell differentiation by 1,25(OH)2D3 is observed at discrete, intermediate stages of mast cell development, identified by expression of c-kit, FcepsilonRI, and IL-3 receptor-alpha chain, and depends on the expression of the vitamin D receptor (VDR). It is important that mast cell progenitors obtained from VDR-ablated mice undergo an accelerated maturation in vitro and give rise to more responsive mast cells than wild-type. Furthermore, histological analysis of mast cell density in peripheral tissues reveals a moderate increase in the number of mast cells in the skin of VDR-deficient mice compared with wild-type animals. These data support the hypothesis of a physiological role of 1,25(OH)2D3 in mast cell development and suggest novel, therapeutic uses of 1,25(OH)2D3 analogs.
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PMID:VDR-dependent regulation of mast cell maturation mediated by 1,25-dihydroxyvitamin D3. 1703 39

The active form of vitamin D (1alpha, 25-dihydroxycholecalciferol; calcitriol) has potent anti-neoplastic activity in the management of a number of human malignancies. Despite promising data to suggest that calcitriol is an effective adjunct to current chemotherapy modalities, the role of calcitriol in animal neoplasia is poorly understood. Vitamin D inhibits growth of canine mast cell tumours (MCTs) in vitro, presumably due to ligand-mediated activation of the vitamin D receptor (VDR). The aim of the present study was to examine immunohistochemically the expression of the VDR by reactive and neoplastic canine cutaneous mast cells. Expression was graded according to frequency, intensity and score (frequency x intensity). VDR expression was found in all samples containing reactive mast cells (n=9), and in 67 of 69 (97%) MCTs selected from each of the three Patnaik grades. The frequency and score of VDR labelling was greater in MCTs compared with reactive mast cells (P=0.0005 and 0.001, respectively). There was no difference in VDR frequency between the MCT grades, but the frequency of labelling in grade 3 MCTs was higher than for reactive mast cells (P=0.001). There was no association between tumour mitotic index and any of the three VDR variables (all P>0.16). VDR is widely expressed by reactive and neoplastic canine mast cells in vivo. VDR expression is unlikely to represent an independent prognostic factor, but its presence within biopsy specimens might be used to identify patients that are suited to high-dose vitamin D therapeutic trials.
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PMID:An immunohistochemical study of vitamin D receptor expression in canine cutaneous mast cell tumours. 2033 72

Calcitriol potentiates the effect of multiple chemotherapy agents in a variety of tumour models. In this study, we examine whether calcitriol increases chemotherapy or tyrosine kinase inhibitor in vitro cytotoxicity in canine mastocytoma C2 cells. We also evaluate the in vivo effect of DN101, a highly concentrated oral formulation of calcitriol designed specifically for cancer therapy, as a single-agent therapy in dogs with mast cell tumours (MCTs). Calcitriol exhibits synergistic, antiproliferative activity when used in combination with CCNU, vinblastine, imatinib or toceranib in vitro. The concentrations required for 50% growth inhibition were generally two- to six-fold lower when the drugs were used in combination than when used individually. High-dose oral calcitriol induced remission in 4 of 10 dogs (one complete remission, three partial remissions), although the majority experienced toxicity, necessitating discontinuation of the trial. Further evaluation of calcitriol in combination therapy for dogs with MCTs is warranted.
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PMID:Calcitriol (1,25-dihydroxycholecalciferol) enhances mast cell tumour chemotherapy and receptor tyrosine kinase inhibitor activity in vitro and has single-agent activity against spontaneously occurring canine mast cell tumours. 2069 Oct 28