Pyrrolidinedithiocarbamate inhibits NF-κB activation and IL-8 production in intestinal epithelial cells

During inflammatory bowel disease and intestinal ischemia, epithelial cells of the gut mucosa produce various inflammatory mediators, including the chemokine interleukin (IL-8). This IL-8 produced by intestinal epithelial cells has recently been implicated as a contributory factor to the deleterious inflammatory process resulting in colitis during inflammatory bowel disease or multiple organ failure following shock and trauma. Recent evidence suggests that the transcription factor nuclear factor κB (NF-κB) is a central regulator of IL-8 gene expression. In the present paper we investigated the effect of pharmacological inhibition of NF-κB with pyrrolidinedithiocarbamate (PDTC) on IL-1β-induced IL-8 production by the human intestinal epithelial cell line HT-29. Pretreatment of cells with PDTC (3-1000 μM) dose-dependently attenuated IL-8 production. Furthermore, PDTC (100 μM) suppressed the accumulation of IL-8 mRNA. PDTC inhibited the activation of NF-κB, because PDTC suppressed both NF-κB DNA binding and NF-κB-dependent transcriptional activity. Taken together, our data demonstrate that NF-κB inhibition with PDTC decreases IL-8 production by intestinal epithelial cells.