Abstract
Our previous report of predominant activation of nuclear transcription factor NF-κB in the bladder urothelium of interstitial cystitis (IC) patients suggests a potential role for this nuclear factor in the pathogenesis of the disease. Although NF-κB has been implicated in the pathogenesis of several inflammatory diseases, the downstream mechanism(s) by which it can mediate its effects are still fragmentary. In this study, we examined the role of this nuclear factor on the induction of proinflammatory cytokine gene expression in human bladder carcinoma T24 cells and further examined their corresponding protein levels in the urine of IC patients. T24 cells transduced with a dominant-negative super-repressor IκB mutant (pAxCAmIκB-M) or wild-type adenoviral vectors in the presence or absence of rhTNF-α. Transduction efficiency and ability of pAxCAmIκB-M to inhibit NF-κB activation were monitored by in situ reporter β-galactosidase and gel mobility shift assays, respectively. Expression profile analysis of proinflammatory cytokines was measured in cells and urine of IC patients using RT-PCR and ELISA, respectively. The activation of NF-κB by rhTNF-α was associated with 27, eight, ten and sevenfold increases in the TNF-α, IL-1β, IL-6 and IL-8 transcripts, respectively. In contrast, abrogation of the TNF-α-induced cytokine gene expression by an adenovirus super-repressor IκB mutant vector demonstrate that these effects were NF-κB-dependent. Interestingly, the NF-κB-induced expression of these transcripts correlates with increased protein levels of NF-κB-regulated proinflammatory factors in the urine of IC patients in comparison to controls. That these factors are capable of activating NF-κB in urothelial cells suggests a pivotal role for this nuclear transcription factor in the pathophysiology of the disease, possibly by inducing aberrant immune and inflammatory responses within the bladder of IC patients.
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An erratum to this article can be found at http://dx.doi.org/10.1007/s00240-004-0422-x
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Abdel-Mageed, A.B. NF-κB-dependent gene expression of proinflammatory cytokines in T24 cells: possible role in interstitial cystitis. Urol Res 31, 300–305 (2003). https://doi.org/10.1007/s00240-003-0339-9
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DOI: https://doi.org/10.1007/s00240-003-0339-9