title: P-glycoprotein in autoimmune rheumatic diseases.
abstract: P-glycoprotein (Pgp) is a transmembrane protein of 170 kD encoded by the multidrug resistance 1 (MDR-1) gene, localized on chromosome 7. More than 50 polymorphisms of the MDR-1 gene have been described; a subset of these has been shown to play a pathophysiological role in the development of inflammatory bowel disease, femoral head osteonecrosis induced by steroids, lung cancer and renal epithelial tumors. Polymorphisms that have a protective effect on the development of conditions such as Parkinson disease have also been identified. P-glycoprotein belongs to the adenosine triphosphate binding cassette transporter superfamily and its structure comprises a chain of approximately 1280 aminoacid residues with an N-C terminal structure, arranged as 2 homologous halves, each of which has 6 transmembrane segments, with a total of 12 segments with 2 cytoplasmic nucleotide binding domains. Many cytokines like interleukin 2 and tumor necrosis factor alpha increase Pgp expression and activity. Pgp functions as an efflux pump for a variety of toxins in order to protect particular organs and tissues as the central nervous system. Pgp transports a variety of substrates including glucocorticoids while other drugs such as tacrolimus and cyclosporine A act as modulators of this protein. The most widely used method to measure Pgp activity is flow cytometry using naturally fluorescent substrates such as anthracyclines or rhodamine 123. The study of drug resistance and its association to Pgp began with the study of resistance to chemotherapy in the treatment of cancer and antiretroviral therapy for human immunodeficiency virus; however, the role of Pgp in the treatment of systemic lupus erythematosus, rheumatoid arthritis and psoriatic arthritis has been a focus of study lately and has emerged as an important mechanism by which treatment failure occurs. The present review analyzes the role of Pgp in these autoimmune diseases.
authors.affiliation: Systemic Autoimmune Diseases Research Unit, Hospital General Regional No. 36, Instituto Mexicano del Seguro Social, Puebla, Mexico; Department of Immunology and Rheumatology, Medicine School, Benemérita Universidad Autónoma dePuebla, Puebla, Mexico. Electronic address: mgc30591@yahoo.com.
authors.forename: M
authors.initials: M
authors.lastname: García-Carrasco
authors.affiliation: Systemic Autoimmune Diseases Research Unit, Hospital General Regional No. 36, Instituto Mexicano del Seguro Social, Puebla, Mexico; Department of Immunology and Rheumatology, Medicine School, Benemérita Universidad Autónoma dePuebla, Puebla, Mexico. Electronic address: cmp_26@yahoo.com.mx.
authors.forename: C
authors.initials: C
authors.lastname: Mendoza-Pinto
authors.affiliation: Systemic Autoimmune Diseases Research Unit, Hospital General Regional No. 36, Instituto Mexicano del Seguro Social, Puebla, Mexico. Electronic address: kartagener@live.com.mx.
authors.forename: S
authors.initials: S
authors.lastname: Macias Díaz
authors.affiliation: Departament of Dermatology, Indisa Clinic Santiago de Chile, Chile. Electronic address: drmauricio.vera@indisa.cl.
authors.forename: M
authors.initials: M
authors.lastname: Vera-Recabarren
authors.affiliation: Departament of Experimental Medicine, Medicine School, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico. Electronic address: lvazdela@yahoo.com.mx.
authors.forename: L
authors.initials: L
authors.lastname: Vázquez de Lara
authors.affiliation: Systemic Autoimmune Diseases Research Unit, Hospital General Regional No. 36, Instituto Mexicano del Seguro Social, Puebla, Mexico. Electronic address: soco_6914@hotmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Méndez Martínez
authors.affiliation: Systemic Autoimmune Diseases Research Unit, Hospital General Regional No. 36, Instituto Mexicano del Seguro Social, Puebla, Mexico. Electronic address: pamss1721@yahoo.com.
authors.forename: P
authors.initials: P
authors.lastname: Soto-Santillán
authors.affiliation: Systemic Autoimmune Diseases Research Unit, Hospital General Regional No. 36, Instituto Mexicano del Seguro Social, Puebla, Mexico. Electronic address: rebekita_@live.com.mx.
authors.forename: R
authors.initials: R
authors.lastname: González-Ramírez
authors.affiliation: Laboratorios Clinicos de Puebla, Puebla, Mexico; Universidad de las Américas Puebla, Mexico. Electronic address: aruiz@clinicaruiz.com.
authors.forename: A
authors.initials: A
authors.lastname: Ruiz-Arguelles
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D006801:Humans; D011110:Polymorphism, Genetic; D012216:Rheumatic Diseases / Q000276:immunology*; D013379:Substrate Specificity
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1
keywords: Flow cytometry; Glucocorticoids; Ineffective therapy; Methotrexate; P-glycoprotein; Psoriatic arthritis; Rheumatoid arthritis; Systemic lupus erythematosus