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Analogs of 1α,25‐dihydroxyvitamin D 3 as pluripotent immunomodulators
Author(s) -
van Etten Evelyne,
Decallonne Brigitte,
Verlinden Lieve,
Verstuyf Annemieke,
Bouillon Roger,
Mathieu Chantal
Publication year - 2003
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10329
Subject(s) - in vivo , vitamin d and neurology , in vitro , immune system , potency , nod , induced pluripotent stem cell , pharmacology , nod mice , calcium , chemistry , adverse effect , diabetes mellitus , medicine , immunology , endocrinology , biology , biochemistry , embryonic stem cell , microbiology and biotechnology , gene
The active form of vitamin D 3 , 1,25(OH) 2 D 3 , is known, besides its classical effects on calcium and bone, for its pronounced immunomodulatory effects that are exerted both on the antigen‐presenting cell level as well as directly on the T lymphocyte level. In animal models, these immune effects of 1,25(OH) 2 D 3 are reflected by a strong potency to prevent onset and even recurrence of autoimmune diseases. A major limitation in using 1,25(OH) 2 D 3 in clinical immune therapy are the adverse side effects on calcium and on bone. TX527 (19‐nor‐14,20‐bisepi‐23‐yne‐1,25(OH) 2 D 3 ) is a structural 1,25(OH) 2 D 3 analog showing reduced calcemic activity associated with enhanced in vitro and in vivo immunomodulating capacity compared to the mother‐molecule. Indeed, in vitro TX527 is more potent that 1,25(OH) 2 D 3 in redirecting differentiation and maturation of dendritic cells and in inhibiting phytohemagglutinin‐stimulated T lymphocyte proliferation. In vivo, this enhanced potency of TX527 is confirmed by a stronger potential to prevent type 1 diabetes in nonobese diabetic (NOD) mice and to prolong the survival of syngeneic islets grafts, both alone and in combination with cyclosporine A, in overtly diabetic NOD mice. Moreover, these in vivo effects of TX527 are obtained without the adverse side effects observed for 1,25(OH) 2 D 3 itself. We believe therefore that TX527 is a potentially interesting candidate to be considered for clinical intervention trails in autoimmune diseases. J. Cell. Biochem. 88: 223–226, 2003. © 2002 Wiley‐Liss, Inc.