Abstract: Autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic inflammatory disorders of unknown etiology characterized by a wide range of abnormalities of the immune system that may compromise the function of several organs, such as kidney, heart, joints, brain and skin. Corticosteroids (CCS), synthetic and biologic immunosuppressive agents have demonstrated the capacity to improve the course of autoimmune diseases. However, a significant number of patients do not respond or develop resistance to these therapies over time. P-glycoprotein (P-gp) is a transmembrane protein that pumps several drugs out of the cell, including CCS and immunosuppressants; thus, its over-expression or hyper-function has been proposed as a possible mechanism of drug resistance in patients with autoimmune disorders. Recently, different authors have demonstrated that P-gp inhibitors, such as cyclosporine A (CsA) and its analogue Tacrolimus, are able to reduce P-gp expression and or function in SLE, RA and PsA patients. These observations suggest that P-gp antagonists could be adopted to revert drug resistance and improve disease outcome. The complex inter-relationship among drug resistance, P-gp expression and autoimmunity still remains elusive.
Keywords: p-glycoprotein; autoimmune diseases; multidrug resistance; lymphocytes
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Picchianti-Diamanti, A.; Rosado, M.M.; Scarsella, M.; Laganà, B.; D'Amelio, R. P-Glycoprotein and Drug Resistance in Systemic Autoimmune Diseases. Int. J. Mol. Sci. 2014, 15, 4965-4976.
Picchianti-Diamanti A, Rosado MM, Scarsella M, Laganà B, D'Amelio R. P-Glycoprotein and Drug Resistance in Systemic Autoimmune Diseases. International Journal of Molecular Sciences. 2014; 15(3):4965-4976.
Picchianti-Diamanti, Andrea; Rosado, Maria M.; Scarsella, Marco; Laganà, Bruno; D'Amelio, Raffaele. 2014. "P-Glycoprotein and Drug Resistance in Systemic Autoimmune Diseases." Int. J. Mol. Sci. 15, no. 3: 4965-4976.