MK4MDD

Pathway Report

Basic Information
Name NF-kB activation by non-typable Haemophilus infuenzae
BioCarta Link ID: NTHI_PATHWAY
Name: nthi pathway
Brief Description: NFkB activation by Nontypeable Hemophilus influenzae
Full Description: 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.
No. of Studies (Positive/Negative) 1 (1/0) Help

Positive relationship between NF-kB activation by non-typable Haemophilus infuenzae and MDD (count: 1)
Name in Literature Reference Research Type Statistical Result Relation Description Help
NF-kB activation by non-typable Haemophilus in?uenzae Kao CF, 2012 patients and normal controls We found 17 significantly enriched pathways for depression We found 17 significantly enriched pathways for depression

Positive relationships between NF-kB activation by non-typable Haemophilus infuenzae and other components at different levels (count: 0) Help
Positive relationship network of NF-kB activation by non-typable Haemophilus infuenzae in MK4MDD
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Note:
1. The different color of the nodes denotes the level of the nodes.
Genetic/Epigenetic Locus Protein and Other Molecule Cell and Molecular Pathway Neural System Cognition and Behavior Symptoms and Signs Environment MDD
Genetic/Epigenetic Locus Protein and Other Molecule Cell and Molecular Pathway Neural System Cognition and Behavior Symptoms and Signs Environment MDD
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3. The network is generated using Cytoscape Web Cytoscape Web
Negative relationships between NF-kB activation by non-typable Haemophilus infuenzae and MDD (count: 0)
Negative relationships between NF-kB activation by non-typable Haemophilus infuenzae and other components at different levels (count: 0) Help
Pathway NF-kB activation by non-typable Haemophilus infuenzae related genes in MK4MDD (count: 8)