| A Nonsecosteroidal Vitamin D Receptor Modulator Ameliorates Experimental Autoimmune Encephalomyelitis without Causing Hypercalcemia. | |
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MedLine Citation:
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PMID: 21318047 Owner: NLM Status: PubMed-not-MEDLINE |
Abstract/OtherAbstract:
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Vitamin D receptor (VDR) agonists are currently the agents of choice for the treatment of psoriasis, a skin inflammatory indication that is believed to involve an autoimmune component. 1,25-dihydroxyvitamin D3 [1,25-(OH)(2)D(3)], the biologically active metabolite of vitamin D, has shown efficacy in animal autoimmune disease models of multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and type I diabetes. However, the side effect of 1,25-(OH)(2)D(3) and its synthetic secosteroidal analogs is hypercalcemia, which is a major impediment in their clinical development for autoimmune diseases. Hypercalcemia develops as a result of the action of VDR agonists on the intestine. Here, we describe the identification of a VDR modulator (VDRM) compound A that was transcriptionally less active in intestinal cells and as a result exhibited less calcemic activity in vivo than 1,25-(OH)(2)D(3). Cytokine analysis indicated that the VDRM not only modulated the T-helper cell balance from Th1 to Th2 effector function but also inhibited Th17 differentiation. Finally, we demonstrate that the oral administration of compound A inhibited the induction and progress of experimental autoimmune encephalomyelitis in mice without causing hypercalcemia. |
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Authors:
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Songqing Na; Yanfei Ma; Jingyong Zhao; Clint Schmidt; Qing Q Zeng; Srinivasan Chandrasekhar; William W Chin; Sunil Nagpal |
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Publication Detail:
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Type: Journal Article Date: 2011-01-26 |
Journal Detail:
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Title: Autoimmune diseases Volume: 2011 ISSN: 2090-0430 ISO Abbreviation: Autoimmune Dis Publication Date: 2011 |
Date Detail:
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Created Date: 2011-02-14 Completed Date: 2011-07-14 Revised Date: 2011-07-25 |
Medline Journal Info:
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Nlm Unique ID: 101546750 Medline TA: Autoimmune Dis Country: England |
Other Details:
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Languages: eng Pagination: 132958 Citation Subset: - |
Affiliation:
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Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. |
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