BTZO-1 selectively bound macrophage migration inhibitory factor, and reduction of cellular MIF protein levels by siRNA suppressed BTZO-1-induced GST Ya expression. Therefore, MIF may be a target protein of BTZO-1. ARE is a cis-acting DNA regulatory element located in the regulatory regions of multiple genes encoding phase II detoxifying enzymes and cytoprotective proteins including GSTs, HO-1, reduced nicotinamide adenine dinucleotide phosphate H), quinone oxidoreductases, UDP-glucuronosyl transferase, epoxide hydrase, c-glutamylcystein synthetase, and peroxiredoxin 1. In mammalian cells, activation of the ARE is of critical importance to cellular protection against oxidative stress. In fact, t-BHQ, which up-regulates a battery of ARE-regulated genes, reportedly protects cells from oxidative damage in vitro. There is also a growing body of evidence suggesting that modulation of these cytoprotective genes has profound effects on immune and inflammatory responses. Thus, coordinate induction of cytoprotective genes via activation of AREs may represent a novel PI-103 therapeutic approach for the treatment of immune and inflammatory diseases. Here we show the cytoprotective effects of BTZO-15, a BTZO1 derivative with favorable absorption-distribution-metabolismelimination-toxicity. BTZO-15 suppressed NOonduced cell death in IEC-18 cell line derived from rat intestinal epithelial cells. BTZO-15 also showed protective effects against dextran sulfate sodium -induced colitis and 2,4,6-trinitrobenzene sulfonic acid -induced colitis in rats. To date, no ARE activator have been used as therapeutic drugs for IBD. The results suggest that ARE activation can be an attractive and novel approach to IBD therapy. The etiology of IBD is still unclear, although there is evidence that oxidative stress plays a role in the pathogenesis of IBD and could be the mainstay of disease initiation and perpetuation. Many agents, such as 5-amino salicylic acid, antibiotics, steroids, immunosuppressive agents, and anti tumor necrosis factor-a, infliximab, are available for IBD therapy; however, they have problems of lower efficacy and/or side effects. For example 5-ASA, a pharmacological standard therapy for UC,, does not exhibit adequate efficacy in maintenance and remission and produces side-effects, such as interstitial nephritis. Antibiotics, steroids, and immunosuppressive agents, including cyclosporine, are powerful therapeutic approaches to avoid sepsis or life-threatening complications in IBD in an acute setting.