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Ikbkb  -  inhibitor of kappa light polypeptide gene...

Rattus norvegicus

Synonyms: AIM-1, I-kappa-B kinase 2, I-kappa-B-kinase beta, IKK-B, IKK-beta, ...
 
 
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Disease relevance of Ikbkb

 

High impact information on Ikbkb

  • The activation of NF-kappaB was inhibited by expression of a "supersuppressor" IkappaBalpha mutant that is resistant to stimulation-induced degradation and a dominant negative IkappaB kinase (IKKbeta) mutant that can no longer be activated by phosphorylation [5].
  • Thus, IKK2 is the main mediator for cytokine-induced NF-kappa B activation in primary hepatocytes and protects against TNF-alpha-induced apoptosis, whereas IKK1 kinase activity is not required for NF-kappa B activation [6].
  • We analyzed the differential role of I kappa B kinase 1 (IKK1) and I kappa B kinase 2 (IKK2) in tumor necrosis factor alpha (TNF-alpha)- and interleukin-1 beta (IL-1 beta)-mediated NF-kappa B activation in primary rat hepatocytes [6].
  • Thus, peroxynitrite has a dual effect on NF-kappaB, inhibiting canonical IKKbeta-dependent NF-kappaB activation while activating NF-kappaB-inducing kinase and IKKalpha phosphorylation, which suggests its involvement in an alternative pathway of NF-kappaB activation [7].
  • Suppression of IKKbeta-dependent NF-kappaB activation translated into a marked inhibition of the transcription of NF-kappaB-dependent genes by peroxynitrite [7].
 

Biological context of Ikbkb

  • Moreover, the activation of IKKalpha, IKKbeta, and NIK by IGF-II was dependent on phosphatidylinositol 3-kinase, a key regulator of myogenesis [8].
  • Phosphatidylinositol 3-kinase/Akt, extracellular signal-regulated kinase 1/2, and IkappaB kinase beta appear to contribute to the anti-apoptotic effect of LPS since the specific inhibitors, wortmannin, PD98059, and dominant negative IKKbeta transgene expression reversed the LPS effect [9].
  • Hypoxia-induced mitochondrial defects and cell death were suppressed in cells expressing IKKbetawt but not in cells expressing the kinase-defective IKKbeta mutant [10].
 

Anatomical context of Ikbkb

  • For this purpose rAAV5 carrying the dominant negative IKK beta gene (AAV5.IKK beta dn) or control AAV5.eGFP was injected into the right ankle joint [1].
  • In conclusion, we are the first to demonstrate that rAAV5 can be used to successfully deliver a therapeutic gene (IKK beta dn) to the synovium, resulting in reduced severity of inflammation in AA in vivo and proinflammatory cytokine production in human RA synovial tissue ex vivo [1].
  • L6E9 myoblasts differentiated with IGF-II showed an induction of NF-kappaB DNA-binding activity that correlated in time with the activation of IKKalpha, IKKbeta, and NIK [8].
  • A dominant negative form of IKK2 prevents suppression of apoptosis by the peroxisome proliferator nafenopin [11].
  • We report in vivo ischemia-reperfusion (I/R)-induced NF-kappaB activation, IkappaB kinase -beta (IKKbeta) activity, and IkappaBalpha phosphorylation and degradation in rat myocardium [3].
 

Associations of Ikbkb with chemical compounds

  • OBJECTIVE: Inhibitor of nuclear factor kappaB kinase beta (IkappaB kinase beta, or IKKbeta) has emerged as a key regulator of the transcription factor nuclear factor kappaB (NF-kappaB) [2].
  • Our results revealed that pretreatment with ISO significantly inhibited Ang II-mediated NF-kappaB through affecting the degradation and phosphorylation of IkappaBalpha and the activity of IKKbeta and AP-1 activation by influencing the expression of c-Fos and c-Jun proteins [12].
  • Treatment with 50 microM of falcarindiol for 60 min diminished the LPS/IFN-gamma-mediated activation of IkappaB kinase-alpha (IKK-alpha) and IKK-beta by 28.2 and 29.7%, respectively [13].
  • We measured NF-kappaB signaling components [NF-kappaB translocation, IkappaBalpha, p65, mRNA and protein levels, and IkappaB kinase-beta (IKKbeta) activity] at 12 and 36 wk in WKYs and SHRs and at 10 wk in PDTC-treated rats (n = 9) [14].
  • In monocytes, O2- increased I kappa B kinase (IKK)-1 and IKK-2 activity (P < 0.05) and p38 and p42/44 activation and phosphorylation, which was reduced by statins [15].
 

Other interactions of Ikbkb

  • Importantly, expression of the supersuppressor IkappaBalpha mutant or the dominant negative IKKbeta mutant blocked the hypertrophic agonist-induced expression of the embryonic gene atrial natriuretic factor and enlargement of cardiomyocytes [5].
 

Analytical, diagnostic and therapeutic context of Ikbkb

  • Consequently, specific targeting of IKK beta in the joint, using gene therapy, presents a sophisticated treatment option for arthritis [1].
  • METHODS: Normal Lewis rats were evaluated for paw swelling by plethysmometry and histologic assessment after intraarticular injection of an adenoviral construct encoding the IKKbeta wild-type gene (Ad.IKKbeta-wt); controls received an adenoviral construct encoding green fluorescent protein (Ad.GFP) [2].
  • In conclusion, we have demonstrated that animal models with similar profiles of airway inflammation can be IKK-2 inhibitor/steroid-sensitive or -insensitive [16].
  • IKKbeta activity was markedly increased in ischemic (1,800%) and nonischemic (860%) areas, and phosphorylated IkappaBalpha levels were significantly elevated in ischemic (180%) and nonischemic (280%) areas at 5 min of ischemia and further increased after reperfusion [3].

References

  1. Amelioration of arthritis by intraarticular dominant negative Ikk beta gene therapy using adeno-associated virus type 5. Tas, S.W., Adriaansen, J., Hajji, N., Bakker, A.C., Firestein, G.S., Vervoordeldonk, M.J., Tak, P.P. Hum. Gene Ther. (2006) [Pubmed]
  2. Inhibitor of nuclear factor kappaB kinase beta is a key regulator of synovial inflammation. Tak, P.P., Gerlag, D.M., Aupperle, K.R., van de Geest, D.A., Overbeek, M., Bennett, B.L., Boyle, D.L., Manning, A.M., Firestein, G.S. Arthritis Rheum. (2001) [Pubmed]
  3. Early activation of IKKbeta during in vivo myocardial ischemia. Li, C., Kao, R.L., Ha, T., Kelley, J., Browder, I.W., Williams, D.L. Am. J. Physiol. Heart Circ. Physiol. (2001) [Pubmed]
  4. Enhancement of lipopolysaccharide-stimulated JNK activity in rat aortic smooth muscle cells by pharmacological and adenovirus-mediated inhibition of inhibitory kappa B kinase signalling. MacKenzie, C.J., Paul, A., Wilson, S., de Martin, R., Baker, A.H., Plevin, R. Br. J. Pharmacol. (2003) [Pubmed]
  5. Activation of NF-kappa B is required for hypertrophic growth of primary rat neonatal ventricular cardiomyocytes. Purcell, N.H., Tang, G., Yu, C., Mercurio, F., DiDonato, J.A., Lin, A. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  6. Differential role of I kappa B kinase 1 and 2 in primary rat hepatocytes. Schwabe, R.F., Bennett, B.L., Manning, A.M., Brenner, D.A. Hepatology (2001) [Pubmed]
  7. Peroxynitrite is a potent inhibitor of NF-{kappa}B activation triggered by inflammatory stimuli in cardiac and endothelial cell lines. Levrand, S., Pesse, B., Feihl, F., Waeber, B., Pacher, P., Rolli, J., Schaller, M.D., Liaudet, L. J. Biol. Chem. (2005) [Pubmed]
  8. Nuclear factor kappa B-inducing kinase and Ikappa B kinase-alpha signal skeletal muscle cell differentiation. Canicio, J., Ruiz-Lozano, P., Carrasco, M., Palacin, M., Chien, K., Zorzano, A., Kaliman, P. J. Biol. Chem. (2001) [Pubmed]
  9. Lipopolysaccharide improves cardiomyocyte survival and function after serum deprivation. Chao, W., Shen, Y., Zhu, X., Zhao, H., Novikov, M., Schmidt, U., Rosenzweig, A. J. Biol. Chem. (2005) [Pubmed]
  10. Nuclear factor-kappaB represses hypoxia-induced mitochondrial defects and cell death of ventricular myocytes. Regula, K.M., Baetz, D., Kirshenbaum, L.A. Circulation (2004) [Pubmed]
  11. A dominant negative form of IKK2 prevents suppression of apoptosis by the peroxisome proliferator nafenopin. Cosulich, S.C., James, N.H., Needham, M.R., Newham, P.P., Bundell, K.R., Roberts, R.A. Carcinogenesis (2000) [Pubmed]
  12. Isorhapontigenin, a new resveratrol analog, attenuates cardiac hypertrophy via blocking signaling transduction pathways. Li, H.L., Wang, A.B., Huang, Y., Liu, D.P., Wei, C., Williams, G.M., Zhang, C.N., Liu, G., Liu, Y.Q., Hao, D.L., Hui, R.T., Lin, M., Liang, C.C. Free Radic. Biol. Med. (2005) [Pubmed]
  13. Falcarindiol impairs the expression of inducible nitric oxide synthase by abrogating the activation of IKK and JAK in rat primary astrocytes. Shiao, Y.J., Lin, Y.L., Sun, Y.H., Chi, C.W., Chen, C.F., Wang, C.N. Br. J. Pharmacol. (2005) [Pubmed]
  14. Inhibition of NF-kappaB induces regression of cardiac hypertrophy, independent of blood pressure control, in spontaneously hypertensive rats. Gupta, S., Young, D., Sen, S. Am. J. Physiol. Heart Circ. Physiol. (2005) [Pubmed]
  15. HMG-CoA reductase inhibitors reduce I kappa B kinase activity induced by oxidative stress in monocytes and vascular smooth muscle cells. Ortego, M., Gómez-Hernández, A., Vidal, C., Sánchez-Galán, E., Blanco-Colio, L.M., Martín-Ventura, J.L., Tuñón, J., Diaz, C., Hernández, G., Egido, J. J. Cardiovasc. Pharmacol. (2005) [Pubmed]
  16. IkappaB kinase-2-independent and -dependent inflammation in airway disease models: relevance of IKK-2 inhibition to the clinic. Birrell, M.A., Wong, S., Hardaker, E.L., Catley, M.C., McCluskie, K., Collins, M., Haj-Yahia, S., Belvisi, M.G. Mol. Pharmacol. (2006) [Pubmed]
 
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