ArticleProceedings of the National Academy of Sciences of the United States of America2004
Synergistic activation of NF-kappaB by nontypeable Haemophilus influenzae and tumor necrosis factor alpha.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 74 citations in OpenAlex.
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- Role of p38 Mitogen-Activated Protein Kinase in Asthma and COPD: Pathogenic Aspects and Potential Targeted Therapies.Drug design, development and therapy · 2021Review
- The Implications of Zinc Therapy in Combating the COVID-19 Global Pandemic.Journal of inflammation research · 2021Review
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- Si-Wei-Qing-Gan-Tang Improves Non-Alcoholic Steatohepatitis by Modulating the Nuclear Factor-κB Signal Pathway and Autophagy in Methionine and Choline Deficient Diet-Fed Rats.Frontiers in pharmacology · 2020Article
- Apoptosis signal-regulating kinase 1 activation by Nox1-derived oxidants is required for TNFα receptor endocytosis.American journal of physiology. Heart and circulatory physiology · 2019Article
- Nontypeable Haemophilus influenzae lysates increase heterogeneous nuclear ribonucleoprotein secretion and exosome release in human middle-ear epithelial cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- The Interplay Between Immune Response and Bacterial Infection in COPD: Focus Upon Non-typeableFrontiers in immunology · 2018Review
- The VP1 unique region of human parvovirus B19 and human bocavirus induce lung injury in naïve Balb/c mice.PloS one · 2018Article
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- Association of microRNA 146 with middle ear hyperplasia in pediatric otitis media.International journal of pediatric otorhinolaryngology · 2016Article
- A proteomic characterization of NTHi lysates.International journal of pediatric otorhinolaryngology · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Nontypeable Haemophilus influenzae (NTHi) is an important human pathogen causing otitis media in children and exacerbation of chronic obstructive pulmonary disease in adults. Like most other bacterial infections, NTHi infections are also characterized by inflammation, which is mainly mediated by cytokines and chemokines such as tumor necrosis factor alpha (TNF-alpha). Among a variety of transcription regulators, NF-kappaB has been shown to play a critical role in regulating the expression of large numbers of genes encoding inflammatory mediators. In review of the current studies on NF-kappaB regulation, most of them have focused on investigating how NF-kappaB is activated by a single inducer at a time. However, in bacteria-induced inflammation in vivo, multiple inducers including both exogenous and endogenous mediators are present simultaneously. A key issue that has yet to be addressed is whether the exogenous inducers such as NTHi and the endogenous factors such as TNF-alpha activate NF-kappaB in a synergistic manner. We show that NTHi and TNF-alpha, when present together, synergistically induce NF-kappaB activation via two distinct signaling pathways: NF-kappaB translocation-dependent and -independent pathways. The NF-kappaB translocation-dependent pathway involves NF-kappaB-inducing kinase-IkappaB kinase beta/gamma-dependent phosphorylation and degradation of IkappaBalpha, whereas the NF-kappaB translocation-independent pathway involves mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase kinase kinase 1-dependent activation of MAPK kinase 3/6-p38 MAPK pathway. In addition, the same signaling pathways are also involved in synergistic induction of TNF-alpha, IL-1beta, and IL-8. These studies should deepen our understanding of the molecular mechanisms underlying the combinatorial regulation of inflammation and lead to development of therapeutic strategies for NTHi-induced infections.
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