| Autor: |
Monroy-Arreola A; Instituto Politécnico Nacional , Unidad Profesional Interdisciplinaria de Biotecnología , Mexico City 07340 , México., Durán-Figueroa NV; Instituto Politécnico Nacional , Unidad Profesional Interdisciplinaria de Biotecnología , Mexico City 07340 , México., Méndez-Flores S; Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán , Mexico City 14080 , México., Domínguez-Cherit J; Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán , Mexico City 14080 , México., Watkinson J; MRC Center for Drug Safety Science , University of Liverpool , Liverpool L69 3GE , United Kingdom., Badillo-Corona JA; Instituto Politécnico Nacional , Unidad Profesional Interdisciplinaria de Biotecnología , Mexico City 07340 , México., Whitaker P; St. James Hospital , Leeds LS9 7TF , United Kingdom., Naisbitt DJ; MRC Center for Drug Safety Science , University of Liverpool , Liverpool L69 3GE , United Kingdom., Castrejón-Flores JL; Instituto Politécnico Nacional , Unidad Profesional Interdisciplinaria de Biotecnología , Mexico City 07340 , México. |
| Abstrakt: |
Dysregulation in the expression of microRNAs (miRNAs), single-stranded RNAs which regulate gene expression, has been associated with diseases such as Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), although their cellular origin has not been explored. Thus, the focus of this work was to study expression patterns of reported miRNAs involved in T-cell activation following drug-specific stimulation in peripheral blood mononuclear cells (PBMCs) and drug-specific CD4 + T-cell clones (TCC) from patients with different cutaneous manifestations of delayed-type drug hypersensitivity reactions. CD4 + T-cells from hypersensitive patients were stimulated to proliferate, secreted cytokines (IFN-γ and IL-22), cytolytic molecules (Granzyme B) and up-regulate miRNAs 24 to 48 h after drug exposure. Carbamazepine-specific CD4 + T-cells that proliferated to the greatest extent and secreted the highest levels of IFN-γ showed an up-regulation of miR-18a and miR-155. In contrast, piperacillin-specific CD4 + T-cells displaying high expression of miR-9 and miR-21 showed an association with the extent of proliferation, but not IFN-γ secretion. MiR-155 up-regulation was detected in PBMCs from all hypersensitive patients 24 h after drug treatment, while miR-18a and miR-21 expression was up-regulated after 48 h. These findings demonstrate that miRNAs are expressed during drug-specific CD4 + T-cell activation and shows a new regulation path for drug hypersensitivity reactions. |
