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Requirements for induction of vitamin D-mediated gene regulation in normal human B lymphocytes.
Morgan, J W; Morgan, D M; Lasky, S R; Ford, D; Kouttab, N; Maizel, A L.
Afiliación
  • Morgan JW; Department of Pathology, Roger Williams Medical Center, Brown University, Providence, RI 02908, USA. John_Morgan@brown.edu
J Immunol ; 157(7): 2900-8, 1996 Oct 01.
Article en En | MEDLINE | ID: mdl-8816395
Mature human lymphocytes are unique targets of 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) in that vitamin D receptors (VDR) are not constitutively expressed, and specific cellular activation signals are required for both the up-regulation of VDR and establishment of reactivity to the lipophilic ligand. Treatment of B lymphocytes with the cytokine IL-4 (IL-4), in the absence of prior activation, induces a weak up-regulation of VDR expression but fails to generate vitamin D-responsive element (VDRE)-reactive nuclear protein complexes or to initiate the genomic transcription of 25-hydroxyvitamin D3 24-hydroxylase. Stimulation of B lymphocytes by either ligation of CD40 Ag or cross-linking the Ig receptor is also insufficient to render B lymphocytes responsive to 1 alpha,25(OH)2D3. However, this apparent lack of response to the secosterol can be overcome by stimulation of B lymphocytes with a combination of these cellular activation signals, which are sufficient to lead to G1 cell cycle progression. In the presence of 1 alpha,25(OH)2D3, cellular activation associated with stimulation of such a progression appears to be sufficient for the up-regulation of VDR message and protein and necessary for the establishment of VDRE binding complexes and the induction of 24-hydroxylase message. Furthermore, biologic functions are modulated, in that the hormone inhibits proliferation in a subset of the activated B cells. These observations suggest that reactivity to 1 alpha,25(OH)2D3 is tightly regulated in B lymphocytes, requiring specific signals for its initiation.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esteroide Hidroxilasas / Calcitriol / Linfocitos B / Regulación de la Expresión Génica / Interleucina-4 / Receptores de Calcitriol / Sistema Enzimático del Citocromo P-450 Límite: Humans Idioma: En Revista: J Immunol Año: 1996 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Buscar en Google
Añadir a Mi BVS
Imprimir
XML
PubMed Links

Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esteroide Hidroxilasas / Calcitriol / Linfocitos B / Regulación de la Expresión Génica / Interleucina-4 / Receptores de Calcitriol / Sistema Enzimático del Citocromo P-450 Límite: Humans Idioma: En Revista: J Immunol Año: 1996 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos