The role of proinflammatory and anti-inflammatory mechanisms in development of resistance mediated by ABC transporters in inflammatory bowel diseases

Savić Mlakar, Ana (2015) The role of proinflammatory and anti-inflammatory mechanisms in development of resistance mediated by ABC transporters in inflammatory bowel diseases. Doctoral thesis, Faculty of Science > Department of Biology.

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Abstract

Efflux transporters are crucial for the maintenance of gut homeostasis and influence drug bioavailability. Changes in their expression can disrupt the barrier which consequently results with inflammatory response, as observed in inflammatory bowel diseases (IBD). Their exact role in IBD pathogenesis is inconclusive. We have measured the expression of transporeters MDR1, MRP1 and BCRP in pediatric and adult patients with Crohn's disease (adults; n=25, pediatric; n=26) and ulcerative colitis (adults; n=27, pediatric; n=20). In paralell, we have assessed the expression of inflammatory cytokines IFN-γ , IL-2, IL-6, IL-1β and IL-17A, as well as their negative regulators, SOCS1 and SOCS3. Subjects were grouped as: newly diagnosed/untreated, active disease/treated, remission and controls (adults; n=10, pediatric; n=15). We showed that altered expression of efflux transporters correlated with cytokine expressions in IBD patients compared to controls. Furthermore, high cytokine expression, followed by high expression of their matched negative regulators, confirmed inflammatory process as the dominant pathological mechanism in IBD. In conclusion, alterations in ABC transporter expression could have functional importance in disease progression and treatment.

Item Type: Thesis (Doctoral thesis)
Keywords: ABC transporters, Crohn's disease, Ulcerative colitis, cytokines, suppressors of cytokine signalling
Supervisor: Svoboda-Beusan, Ivna and Bendelja, Krešo
Date: 2015
Number of Pages: 91
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Silvana Šehić
Date Deposited: 17 Jul 2015 11:39
Last Modified: 17 Jul 2015 11:39
URI: http://digre.pmf.unizg.hr/id/eprint/4141

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