[Intestinal tissue kallikrein-kinin system in patients with ulcerative colitis during treatment with cyclosporine A].
Kinins are mediators of inflammation and proliferation and act by activating their specific B1 and B2 receptors. In the present study we evaluate the tissue kallikrein-kinin system during cyclosporine A treatment in patients with ulcerative colitis (UC). Six severe active UC patients were treated with cyclosporine A, i.v. 4 mg/kg/d by 7 days with clinical improvement. During sigmoidoscopy biopsy specimens were taken in 0, 5, 7 day of the treatment. The genes expression for tissue kallikrein, kallistatin, B1 and B2 receptors were evaluated by QRT-PCR analysis using TaqMan detector. There was no statistically significant difference in the expression of these genes during treatment with cyclosporine A. In addition, genes encoding kallistatin as well as B1 and B2 receptors were investigated in CaCo cells cultures after exposure with cyclosporine A (200-800 ng/ml) in vitro. In vitro mRNA for B1 receptors was significantly higher using therapeutic (200-400 ng/ml) concentration of cyclosporine A, whereas expression of B2 receptor and kallistatin increased after exceeding therapeutic concentration (400-800 ng/ml).Thus, treatment of UC with cyclosporine A seems to be safe in relation to tissue kallikrein-kinin system profile.
Stadnicki
Antoni
A
Katedry i Oddziału Klinicznego Chorób Wewnetrznych Wojewódzkiego Szpitala Specjalistycznego nr 5, Slaskiej Akademii Medycznej w Katowicach.
Gil
Dariusz
D
Mazurek
Urszula
U
Latocha
Małgorzata
M
D018938:Caco-2 Cells; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000378:metabolism; D012809:Colon, Sigmoid / Q000187:drug effects* / Q000378:metabolism; D016572:Cyclosporine / Q000008:administration & dosage*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D016234:Kallikrein-Kinin System / Q000187:drug effects*; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D043783:Receptor, Bradykinin B1 / Q000187:drug effects*; D043782:Receptor, Bradykinin B2 / Q000187:drug effects*; D012812:Sigmoidoscopy; D013997:Time Factors
D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D016572:Cyclosporine