TY - JOUR
T1 - Up-Regulation of T-Cell Activation MicroRNAs in Drug-Specific CD4 + T-Cells from Hypersensitive Patients
AU - Monroy-Arreola, Alejandra
AU - Durán-Figueroa, Noé V.
AU - Méndez-Flores, Silvia
AU - Domínguez-Cherit, Judith
AU - Watkinson, Joel
AU - Badillo-Corona, Jesús A.
AU - Whitaker, Paul
AU - Naisbitt, Dean J.
AU - Castrejón-Flores, José L.
N1 - Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/6/18
Y1 - 2018/6/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85046490115&partnerID=8YFLogxK
U2 - 10.1021/acs.chemrestox.7b00330
DO - 10.1021/acs.chemrestox.7b00330
M3 - Artículo
C2 - 29644860
SN - 0893-228X
VL - 31
SP - 454
EP - 461
JO - Chemical Research in Toxicology
JF - Chemical Research in Toxicology
IS - 6
ER -