Format

Send to

Choose Destination
Int J Mol Sci. 2014 Mar 20;15(3):4965-76. doi: 10.3390/ijms15034965.

P-glycoprotein and drug resistance in systemic autoimmune diseases.

Author information

1
Department of Medical Sciences, Sapienza University of Rome, 2nd School of Medicine, Sant' Andrea University Hospital, 00189 Rome, Italy. pyke@inwind.it.
2
Research Center Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Roma, Italy. manuelaanjosm.rosado@gmail.com.
3
Research Center Ospedale Pediatrico Bambino Gesù, IRCSS, Piazza S. Onofrio 4, 00165 Roma, Italy. marco@libero.it.
4
Department of Medical Sciences, Sapienza University of Rome, 2nd School of Medicine, Sant' Andrea University Hospital, 00189 Rome, Italy. blagana@infinito.it.
5
Department of Medical Sciences, Sapienza University of Rome, 2nd School of Medicine, Sant' Andrea University Hospital, 00189 Rome, Italy. raffaele.damelio@uniroma1.it.

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.

PMID:
24658440
PMCID:
PMC3975434
DOI:
10.3390/ijms15034965
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI) Icon for PubMed Central
Loading ...
Support Center