Bronchiolitis obliterans syndrome is associated with increased p-glycoprotein expression and loss of glucocorticoid receptor from steroid-resistant proinflammatory CD8+ T cells
Clinical and Experimental Immunology May 02, 2018
Hodge G, et al. - With respect to lymphocyte steroid resistance following lung transplant, researchers have shown loss of glucocorticoids (GC) receptor [(GCR)] from the CD8+ cells and they hypothesized that the drug membrane efflux pump, p-glycoprotein-1 (Pgp), may also be involved. In blood lymphocytes from 15 stable lung transplant patients, 10 patients with bronchiolitis obliterans syndrome (BOS) and 10 healthy aged-matched controls (± prednisolone ± Pgp inhibitor, cyclosporin A ± GCR activator, Compound A), Pgp/GCR expression and interferon (IFN)-γ/tumour necrosis factor (TNF)-α proinflammatory cytokine production was measured. BOS was found to be related to increased Pgp expression and loss of GCR from steroid-resistant proinflammatory CD8+ T cells. Graft survival could be improved by treatments that inhibit Pgp and up-regulate GCR in CD8+ T cells.
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