NFKB Activation Pathway

Preferred Label : NFKB Activation Pathway;

NCIt related terms : NFkB activation by Nontypeable Hemophilus influenzae;

Alternative definition : BIOCARTA: The role of Hemophilus influenzae in ear infections and chronic obstructive pulmonary disease includes the induction of an inflammatory response through activation of the transcription factor NF-kB. In addition to activation of inflammatory cytokine genes like IL-1 and TNF, H. influenzae activates TLR2 expression and genes involved in mucus production. Hemophilus influenzae activates NF-kB by multiple mechanisms, starting with activation of the Toll-like receptor 2 (TLR2) by the p16 protein in the H. influenzae outer membrane. TLR2 plays a key role in innate immune responses and is expressed in high levels in lymphoid cells as well as low levels in epithelial cells. The role of TLR2 was supported by blocking NF-kB activation with a dominant negative TLR2 and increasing it with transfection of a normal TLR2 gene. TLR2 in turn activates TAK1, which activates two divergent signaling 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. In the alternate pathway, TAK1 also activates NF-kB through a Map kinase pathway, activating p38 and NF-kB in a nuclear translocation independent manner. Investigation of the mechanisms of H. influenzae signaling involved in NF-kB activation may provide the information needed to develop better treatments for inflammatory conditions caused by this pathogen. Other pathways modulate the role of NF-kB in H. influenzae pathogenesis. Glucocorticoids, widely used as anti-inflammatory drugs, increase TLR2 activation by H. influenzae through the NIK/I-kB kinase pathway, while they repress the p38 dependent activation of NF-kB. The repression of the p38 pathway by glucocorticoids occurs through activation of the MAP kinase phosphatase-1 (MKP-1) which dephosphorylates and deactivates p38. Another aspect of the inflammatory response to H. influenzae infection is the production of excessive mucus, contributing to the overall symptoms of infection. NF-kB activation of the Muc2 gene contributes to mucus overproduction, in addition to H. influenzae activation of the TGF-beta receptor, activating SMAD transcription factors SMAD3 and SMAD4. Understanding mechanisms that modify H. influenzae signaling will contribute to further understanding the pathogenesis and treatment of ear infections and chronic obstructive pulmonary disease. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_nthiPathway;

Details

Origin ID

C39173;

UMLS CUI

C1513837;

Semantic type(s)
- Molecular Function [UMLS semantic type]
has_gene_product_element
- CREB-Binding Protein [NCIt concept]
- Desmoplakin [NCIt concept]
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 3 [NCIt concept]
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 6 [NCIt concept]
- Dual Specificity Protein Phosphatase 1 [NCIt concept]
- Glucocorticoid Receptor [NCIt concept]
- Histone Acetyltransferase p300 [NCIt concept]
- Inhibitor of Nuclear Factor Kappa-B Kinase Subunit Alpha [NCIt concept]
- Interleukin-1 Beta [NCIt concept]
- Interleukin-8 [NCIt concept]
- Mitogen-Activated Protein Kinase 11 [NCIt concept]
- Mitogen-Activated Protein Kinase 14 [NCIt concept]
- Mitogen-Activated Protein Kinase Kinase Kinase 14 [NCIt concept]
- Mitogen-Activated Protein Kinase Kinase Kinase 7 [NCIt concept]
- Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 [NCIt concept]
- Mothers Against Decapentaplegic Homolog 3 [NCIt concept]
- Mothers Against Decapentaplegic Homolog 4 [NCIt concept]
- Mucin-2 [NCIt concept]
- NF-Kappa-B Inhibitor Alpha [NCIt concept]
- TGF-Beta Receptor Type-1 [NCIt concept]
- TGF-Beta Receptor Type-2 [NCIt concept]
- Toll-Like Receptor 2 [NCIt concept]
- Transcription Factor p65 [NCIt concept]
- Tumor Necrosis Factor [NCIt concept]
pathway_has_gene_element
- CHUK wt Allele [NCIt concept]
- CREBBP wt Allele [NCIt concept]
- CXCL8 wt Allele [NCIt concept]
- DSP wt Allele [NCIt concept]
- DUSP1 wt Allele [NCIt concept]
- EP300 wt Allele [NCIt concept]
- IL1B wt Allele [NCIt concept]
- MAP2K3 wt Allele [NCIt concept]
- MAP2K6 wt Allele [NCIt concept]
- MAP3K14 wt Allele [NCIt concept]
- MAP3K7 wt Allele [NCIt concept]
- MAP4K4 wt Allele [NCIt concept]
- MAPK11 wt Allele [NCIt concept]
- MAPK14 wt Allele [NCIt concept]
- MUC2 wt Allele [NCIt concept]
- NFKBIA wt Allele [NCIt concept]
- NR3C1 wt Allele [NCIt concept]
- RELA wt Allele [NCIt concept]
- SMAD3 wt Allele [NCIt concept]
- SMAD4 wt Allele [NCIt concept]
- TGFBR1 wt Allele [NCIt concept]
- TGFBR2 wt Allele [NCIt concept]
- TLR2 wt Allele [NCIt concept]
- TNF wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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