316 induced by cytokines in IECs, and this is mainly dependent on the κB-2 site present in its promoter. Moreover, IFN-γ- induced CXCL10 mRNA and protein secretion was inhibited upon NF-kB inhibition. Although the present results may reflect only a small aspect in the overall concert of chemokines, it seems apparent that the basic regulatory principles elucidated here might be shared also by a number of other chemokine genes like that of CCL19, which has recently been shown to be regulated by multiple NF-κB and IRF family transcription factors in human monocyte-derived dendritic cells [44]. Recently, Hiroi M et.al. [45] showed that co- operation between IFN-γ induced STAT1, and the consti- tutively active or inducible NF-κB is necessary for the transcriptional activity of IFN-γ-inducible genes like MIG and CXCL10. Therefore, we suggest a similar mechanism for IFN-γ-induced CXCL10 in IECs. The responsiveness to cytokines might depend on the state of differentiation. Schlottmann et. al. [46] recently showed that in contrast to HT29 where IFNγ up-regulated CXCL8 secretion, the same was unaffected in Caco-2 cells or even down-regulated in primary colonic epithelial cells. Future studies on chemokine regulation should therefore include primary cells, keeping well in mind that the presence of contaminating immune cells, culture conditions and cell stress during isolation may influence results. Taken together, our data suggest that while IFN-γ, TNF- α and IL-1β may work individually through disparate signalling pathways in CXCL10 gene regulation, a combi- nation of these cytokines enhances transcription of the CXCL10 gene in an NF-κB-dependent manner. The fact that IL-1β via activation of NF-κB is able to mimic the effect of TNF-α in augmenting CXCL10 expression might be of importance in patients with IBD, who do not respond to anti TNF-α antibody therapy. In those cases, an additional inhibition of IL-1β might be desirable as a future therapy option in treating IBD. 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