Disease relevance of Ikbkb

• In the present study we investigated the effect of inhibiting IKK beta in adjuvant arthritis (AA) in rats, using recombinant adeno-associated virus (rAAV)-mediated intraarticular gene therapy [1].
• For studies of the effects of inhibition of IKKbeta activity, Lewis rats were immunized with Mycobacterium tuberculosis in mineral oil [2].
• Since IKKbeta could have both pro- and antiinflammatory activity, we examined whether its constitutive activation was sufficient to cause a chronic inflammatory disease such as rheumatoid arthritis [2].
• Early activation of IKKbeta during in vivo myocardial ischemia [3].
• 4. Infection of RASMCs with an adenovirus encoding either inhibitory kappa Balpha or a dominant-negative IKKbeta potentiated LPS-stimulated JNK activity [4].

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