Abstract：
: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.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Monroy-Arreola A,Durán-Figueroa NV,Méndez-Flores S,Domínguez-Cherit J,Watkinson J,Badillo-Corona JA,Whitaker P,Naisbitt DJ,Castrejón-Flores JLdoi
10.1021/acs.chemrestox.7b00330subject
Has Abstractpub_date
2018-06-18 00:00:00pages
454-461issue
6eissn
0893-228Xissn
1520-5010journal_volume
31pub_type
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