Nuclear factor kappa B: important transcription factor and therapeutic target.
Nuclear factor kappa B (NF-kappa B) is an ubiquitous rapid response transcription factor in cells involved in immune and inflammatory reactions, and exerts its effect by expressing cytokines, chemokines, cell adhesion molecules, growth factors, and immunoreceptors. In this manner, NF-kappa B contributes to immunologically mediated diseases such as allograft rejection, rheumatoid arthritis, and bronchial asthma. The prototypic inducible form of NF-kappa B is a heterodimer composed of NF-kB1 and RelA, which both belong to the NF-kappa B/Rel family of proteins. Inactive NF-kappa B is present in the cytoplasm complexed with an inhibitory protein, I kappa B. NF-kappa B is activated by a number of incoming signals from the cell surface. Released from I kappa B inhibition, NF-kappa B translocates into the nucleus and binds to the kappa B motif of the target gene. The NF-kappa B activation process can be inhibited by pharmacologic agents at each activation step. Glucocorticoids inhibit NF-kappa B by directly associating with NF-kappa B or by upregulating I kappa B expression. Cyclosporine and tacrolimus prevent NF-kappa B activation by inhibiting the action of calcineurin, a phosphatase that indirectly induces I kappa B degradation. Deoxyspergualin inhibits NF-kappa B by blocking its nuclear translocation. Aspirin and salicylates inhibit upstream events inducing I kappa B phosphorylation. Tepoxalin and antioxidants inhibit NF-kappa B activation by influencing the redox state of the cell. Further research is required to develop more specific inhibitors to treat diseases mediated by NF-kappa B.
Lee
J I
JI
Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh 15261, USA.
Burckart
G J
GJ
D005786:Gene Expression Regulation; D006801:Humans; D007154:Immune System Diseases / Q000188:drug therapy / Q000235:genetics; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000502:physiology
D016328:NF-kappa B; D014157:Transcription Factors