Differences in P-glycoprotein-170 expression and activity between Crohn's disease and ulcerative colitis.
The clinical benefit of Cyclosporine A (CsA) in IBD is controversial. Drugs including CsA are substrates of the P-glycoprotein-170 (Pgp-170) cell surface pump. Although the mechanism of action of CsA is complex, we determined that Pgp-170 might be expressed differentially between these two diseases. Intra-epithelial, lamina propria and peripheral blood lymphocytes were stained with the antibody MRK-16, which recognizes the surface antigen Pgp-170. Functional activity was assayed using a Rhodamine dye efflux assay (Rh123). RT-PCR was used to detect Pgp-170 mRNA. Overall, less P-gp-170 surface expression was found on UC CD3+ intestinal lymphocytes compared to controls and Crohn's disease. A decrease in Pgp-170 activity was also measured using the Rh123 functional assay. Fewer CD8+ intraepithelial lymphocytes (IEL) (which intrinsically have more Pgp-170 function) were also found in UC. Furthermore, UC IEL P-gp expression was under the limit of detection by RT-PCR. Overall, greater and differential expression, function and mRNA for Pgp-170 was found in Crohn's disease compared to the UC and normal tissues analyzed.
Yacyshyn
B
B
Department of Medicine, University of Alberta, Edmonton, Canada. bruce.yacyshyn@ualberta.ca
Maksymowych
W
W
Bowen-Yacyshyn
M B
MB
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000276:immunology / Q000378:metabolism*; D003424:Crohn Disease / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017252:CD3 Complex; D012333:RNA, Messenger