MDR1 mRNA Expressions in Peripheral Blood Mononuclear Cells of Patients with Ulcerative Colitis in Relation to Glucocorticoid Administration

Abstract

Overexpression of multidrug resistance (MDR) protein, P-glycoprotein (P-gp), on lymphocytes has been suggested to be implicated in the failure of glucocorticoid (GC) therapy in patients with ulcerative colitis (UC). However, whether the overexpression of P-gp in a class of patients with inflammatory bowel disease (IBD) is intrinsic or related to the administration of GC is unknown. Relative amounts of MDR1 mRNA expressed in peripheral blood mononuclear cells (PBMCs) were measured using the reverse-transcriptase polymerase chain reaction (RT-PCR) technique in 25 UC patients having no history of GC administration, 25 UC patients having experienced GC therapy, 19 patients with Crohn's disease (CD) with no history of GC therapy, and 27 healthy subjects. Relative amounts of MDR1 mRNA expressed in PBMCs were compared among the groups. The relationship between the amounts of MDR1 mRNA expressed, as well as the total dose of GC administered or the period of GC therapy in UC patients, was examined. The relative amounts of MDR1 mRNA expressed in PBMCs were not significantly different between the healthy subjects and CD patients or UC patients having no history of GC therapy. However, the mean MDR1 mRNA amount in PBMCs of UC patients having experienced GC therapy was significantly greater than that in PBMCs of UC patients with no history of GC administration (p = 0.0375). The amounts of MDR1 mRNA in PBMCs of UC patients having experienced GC therapy significantly correlated with the total dose of GCs administered (p = 0.0175). Overexpression of MDR1 mRNA in PBMCs of IBD patients is not intrinsic. However, high-dose administration of GCs for the treatment of UC may result in an increased expression of MDR1 mRNA, which may impair successful GC therapy in these patients.

P-glycoprotein function in peripheral T lymphocyte subsets of myasthenia gravis patients: Clinical implications and influence of glucocorticoid administration

“…It has been reported that long-term or high-dose administration of GCs for the treatment of autoimmune diseases results in an increased expression of MDR1 mRNA [16] and its related protein [15] in PBMCs, which may impair successful GC therapy in these patients. We also suggest there is a significant correlation between P-gp function in T lymphocytes and prednisolone dose for treatment in this study.…”

“…Furthermore, overexpression of P-gp in PBMCs has been suggested to be related to the administration of GCs for the treatment of patients with rheumatoid arthritis or ulcerative colitis [15,16]. Thus, the present study was undertaken to examine the influence of GC treatment on the P-gp function of T cell subpopulations in PBMCs, and the relationship between P-gp function and clinical response to GC therapy in MG patients.…”

Cellular pharmacodynamics of immunosuppressive drugs for individualized medicine

“…P-gp over-expression has also been reported in the PBMCs of UC patients who are refractory to GC therapy as compared to PBMCs in patients who have responded well to GC therapy [157]. MDR1 mRNA encoding this protein have been suggested to increase in relation to GC administration in the PBMCs of UC patients [158].…”

Persistent expression and function of P-glycoprotein on peripheral blood lymphocytes identifies corticosteroid resistance in patients with systemic lupus erythematosus

“…However, the role of P-gp function in other diseases has received less attention. In ulcerative colitis patients, amount of MDR1 mRNA in peripheral blood mononuclear cells (PBMCs) significantly correlated with the total dose of CS administered [21]. P-gp expression in peripheral lymphocytes correlated with total prednisone dose in children with nephrotic syndrome [13].…”