Nfkb activation pathways

One of these pathways leads to IkB kinase activation, IkB phosphorylation, and degradation, releasing the NF-kB heterodimer to translocate into the nucleus and activate transcription of target genes. Investigation of the mechanisms of H.

Other pathways modulate the role of NF-kB in H. Glucocorticoids, widely used as anti-inflammatory drugs, increase TLR2 activation by H. The repression of the p38 pathway by glucocorticoids occurs through activation of the MAP kinase phosphatase-1 MKP-1 which dephosphorylates and deactivates p Another aspect of the inflammatory response to H.

NF-kB activation of the Muc2 gene contributes to mucus overproduction, in addition to H. Understanding mechanisms that modify H. Genes Dev. Nat Immunol. Chen ZJ. Nat Cell Biol. RIP1, a kinase on the crossroads of a cell's decision to live or die. Cell Death Differ. PIDD: a switch hitter. Mol Cell. Mol Cell Biol. Trends Biochem Sci. Aggarwal BB.

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Toxicol Lett. Infections as a major preventable cause of human cancer. J Intern Med. Perkins ND. Trends Cell Biol. Chen F, Castranova V. TLRs represent a germline encoded nonself recognition system that is hardwired to trigger inflammation Akira et al. However, there is some suggestion that endogenous ligands may trigger TLRs during tissue injury and certain disease states, which may act to promote inflammation in the absence of infection Karin et al.

These pathways are characterized by the differential requirement for IKK subunits. Activation of the alternative pathway regulates genes required for lymph-organogenesis and B-cell activation. Adapted from Tak and Firestein Using radiation chimeras, Alcamo et al. The resulting breakdown in epithelial barrier integrity leads to increased inflammation because of commensal bacteria activating tissue macrophages Chen et al.

More recently, Greten et al. In addition, Greten et al. M2 macrophages are also thought to be important in promoting inflammation-associated cancer Mantovani et al. Hagemann et al. Interestingly, Saccani et al. A homodimeric complex of p50 was found in resting T cells and reduced p50 expression was observed after T-cell activation. Furthermore, overexpression of p50 was shown to repress IL-2 expression in T cells Kang Later studies have shown that colitis was associated with increased ILp40 expression in the colon Tomczak et al.

Apoptosis is an essential mechanism that prevents prolonged inflammation: Neutrophil apoptosis during acute inflammation and activation induced cell death AICD of antigen-specific T cells are important mechanisms that limit inflammatory and immune responses Lawrence and Gilroy Cytokine ; 76 : — Inflammatory bowel disease.

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A20 controls intestinal homeostasis through cell-specific activities. Nat Commun ; 5 : Local administration of antisense phosphorothioate oligonucleotides to the p65 subunit of NF-kappa B abrogates established experimental colitis in mice. Nat Med ; 2 : — Treatment of murine Th1- and Th2-mediated inflammatory bowel disease with NF-kappa B decoy oligonucleotides. IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer.

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J Neuroinflammation ; 9 : Mol Neurodegener ; 11 : Inhibition of transcription factor NF-kappaB in the central nervous system ameliorates autoimmune encephalomyelitis in mice. Nat Immunol ; 7 : — Transgenic inhibition of astroglial NF-kappaB protects from optic nerve damage and retinal ganglion cell loss in experimental optic neuritis. Transgenic inhibition of astroglial NF-kappa B improves functional outcome in experimental autoimmune encephalomyelitis by suppressing chronic central nervous system inflammation.

Progress and challenges in translating the biology of atherosclerosis. Nuclear factor-kappaB activation as a pathological mechanism of lipid metabolism and atherosclerosis. Adv Clin Chem ; 70 : 1— Canonical pathway of nuclear factor kappa B activation selectively regulates proinflammatory and prothrombotic responses in human atherosclerosis. Endothelial cell-specific NF-kappaB inhibition protects mice from atherosclerosis.

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Atherosclerosis ; : — Myeloid IkappaBalpha deficiency promotes atherogenesis by enhancing leukocyte recruitment to the plaques. PLoS One ; 6 : e Myeloid-specific IkappaB kinase beta deficiency decreases atherosclerosis in low-density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol ; 32 : — The NF-kappaB activation pathways, emerging molecular targets for cancer prevention and therapy.