Activation of certain cytokines and adhesion molecules has been postulated being involved in the pathogenesis of experimental and human glomerulonephritis. In this study, we examined whether the transcription factor, nuclear factor ĸB (NFĸB), mediated the expression of these genes involved with the inflammatory response of mesangial cells by using transcription factor decoy oligodeoxynucleotides (ODN) to block NFĸB binding to the promoter site of its target genes. We hypothesized that the NFĸB decoy ODN can inhibit the coordinated activation of cytokines and adhesion molecules induced by TNF-α. Increased binding activity of NFĸB induced by TNF-α was effectively blocked by the NFĸB decoy ODN. TNF-α stimulated CAT expression, which was significantly inhibited by transfection of NFĸB, but not by scrambled decoy ODN. Of importance, NFĸB, but not scrambled decoy ODN, significantly attenuated the increase in RNA and protein levels of IL-1α, IL-1β, IL-6, ICAM-1 and VCAM-1 induced by TNF-α assessed by RT-PCR. Moreover, in vivo transfection of NFĸB decoy ODN inhibited expressions of these cytokines and adhesion molecules induced by TNF-α injection. These results suggest a novel therapeutic strategy for the treatment of glomerulonephritis using decoy ODN to block the binding of NFĸB, inhibiting the coordinated transactivation of the key cytokines and adhesion molecules, and thereby suppressing the inflammatory process.