Deficient apoptosis of activated T cells can result in immunological disorders. Molecules associated with energy and metabolisms are suggested to be involved in pathogenesis of immune diseases, but remain uninvestigated. In the present study we reported that glibenclamide exerted a new pharmacological effect on inflammatory responses by selectively triggering apoptosis of activated T cells. Glibenclamide demonstrated an inhibition on activated T lymphocytes, whereas showed no toxicity in the naive cells. This effect was mainly related with its ability to facilitate apoptosis in activated T cells with an up-regulation of cleaved-caspases and cleaved-PARP. Glibenclamide enhanced Fas expression and suppressed the expression of antiapoptotic cellular FLICE-inhibitory protein. The underlying mechanism of glibenclamide was not associated with its classical inhibitory effect on ATP-sensitive potassium channels, but due to a unique suppression on the phosphorylation of 5' adenosine monophosphate-activated protein kinase, which was augmented during T cell activation. An in vivo experiment further demonstrated that glibenclamide ameliorated T-cell-mediated contact hypersensitivity in mice. Altogether, these results suggest that AMPK inhibition by glibenclamide can regulate the survival and death of T lymphocytes and be beneficial for the treatment of autoimmune diseases.
Keywords: 5-HD (PubChem CID: 23676659); AICAR (PubChem CID: 17513); AMPK; Apoptosis; Compound C (PubChem CID: 11524144); Contact hypersensitivity; Cromakalim (PubChem CID: 71191); Cyclosporin A (PubChem CID: 5284373); Glibenclamide; Glibenclamide (PubChem CID: 3488); K(ATP); Repaglinide (PubChem CID: 65981); T lymphocytes.
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