Inhibition of Interleukin-1-stimulated NF-κB RelA/p65 Phosphorylation by Mesalamine Is Accompanied by Decreased Transcriptional Activity

Abstract

Nuclear factor B (NF-B) is an inducible transcription factor that regulates genes important in immunity and inflammation. The activity of NF-B is highly regulated: transcriptionally active NF-B proteins are sequestered in the cytoplasm by inhibitory proteins, IB.

Inhibitors of NF-κB signaling: 785 and counting

“…Similar to those chemical inhibitors, the natural products mesalamine, mesuol and pertussis toxin appear to specifically block RelA phosphorylation, which is required for optimal RelA-mediated transactivation (Egan et al, 1999;Iordanskiy et al, 2002: Marquez et al, 2005. Moreover, the antiapoptosis protein Bcl-2 was shown to specifically inhibit transactivation by RelA in one study (Grimm et al, 1996), and antithrombin was reported to inhibit NF-kB transactivation by interfering with RelA-CREB co-activator interaction (Uchiba et al, 2004).…”

Role of curcumin and the inhibition of NF-κB in the onset of chemotherapy-induced mucosal barrier injury

“…[42][43][44] CAPE modifies the NF-kB protein so that it can no longer bind to DNA without any effect on IkBa phosphorylation or IkBa degradation. 31,45 Perhaps, by inhibiting the phosphorylation and degradation of IkBa, degradation of other proteins are also inhibited, whereas the inhibition of NFkB binding to DNA could induce apoptosis. The difference in the NF-kB inhibitor pathway and response to chemotherapyinduced cell death is currently under investigation.…”

Mechanism of cytosine arabinoside-mediated apoptosis: role of Rel A (p65) dephosphorylation

“…The p50-p65 heterodimer binds with a specific sequence in DNA, which in turn results in gene transcription. Phosphorylation of p65 of NF-kB (RelA) is required for effective NF-kB-dependent gene transcription (Egan et al, 1999). In this study, time course-dependent increase or decrease in NF-kB levels in nuclear extracts has been referred to as upregulation or downregulation of NF-kB, respectively.…”