Profiling of ABC transporters during active ulcerative colitis and in vitro effect of inflammatory modulators

Inflammatory bowel disease is characterized by chronic inflammation of the gastro intestinal tract that manifests as ulcerative colitis and Crohn's disease. Comparative expression profiles of selected ABC transporter genes during active ulcerative colitis and intestinal tuberculosis were studied, and we also investigated the effect of inflammatory modulators on the expression of the transporters in HT-29 cells.

Using the GEO database, we selected ABC transporter genes that are differentially regulated during active UC and validated the altered expression in biopsies samples by RT-PCR. We also analyzed the effect of inflammatory modulators like TNF-α, lipopolysaccharides (LPS) and drugs (5-ASA, prednisolone and hydrocortisone) on the expression of ABCA1, ABCB8, ABCF2 and ABCC4 using HT-29 cells.

We observed significant up-regulation of ABCA1 and ABCA3 while ABCF2, ABCC6, ABCB8 and ABCC4 were down-regulated during UC. ABCC4 was up-regulated in ITB but down-regulated in UC, whereas others showed similar patterns both in UC and ITB. Upon stimulation of HT29 cells by TNF-α, up-regulation of ABCA1, ABCB8, ABCF2 and ABCC4 was seen, and further using inhibitors we found that it was mediated through reactive oxygen species or NF-kB or both. LPS caused a dose dependent and significant down-regulation of ABCB8, ABCF2 and ABCC4 without any effect on ABCA1. The cells treated with drugs 5-ASA, prednisolone and hydrocortisone, exhibited up-regulation of transporters only at a higher dose.

Altered expression of the above transporters may be associated with the disease. The study also hints at possible mechanisms of differential expression.