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Synergistic activation of NF-kappaB by nontypeable H. influenzae and S. pneumoniae is mediated by CK2, IKKbeta-IkappaBalpha, and p38 MAPK
- Source :
- Biochemical and biophysical research communications. 351(2)
- Publication Year :
- 2006
-
Abstract
- In review of the past studies on NF-kappaB regulation, most of them have focused on investigating how NF-kappaB is activated by a single inducer at a time. Given the fact that, in mixed bacterial infections in vivo, multiple inflammation inducers, including both nontypeable Haemophilus influenzae (NTHi) and Streptococcus pneumoniae, are present simultaneously, a key issue that has yet to be addressed is whether NTHi and S. pneumoniae simultaneously activate NF-kappaB and the subsequent inflammatory response in a synergistic manner. Here, we show that NTHi and S. pneumoniae synergistically induce NF-kappaB-dependent inflammatory response via activation of multiple signaling pathways in vitro and in vivo. The classical IKKbeta-IkappaBalpha and p38 MAPK pathways are involved in synergistic activation of NF-kappaB via two distinct mechanisms, p65 nuclear translocation-dependent and -independent mechanisms. Moreover, casein kinase 2 (CK2) is involved in synergistic induction of NF-kappaB via a mechanism dependent on phosphorylation of p65 at both Ser536 and Ser276 sites. These studies bring new insights into the molecular mechanisms underlying the NF-kappaB-dependent inflammatory response in polymicrobial infections and may lead to development of novel therapeutic strategies for modulating inflammation in mixed infections for patients with otitis media and chronic obstructive pulmonary diseases.
- Subjects :
- Cell Nucleus
Inflammation
Mice, Inbred BALB C
Pyridines
Active Transport, Cell Nucleus
Imidazoles
NF-kappa B
Transcription Factor RelA
Haemophilus influenzae
p38 Mitogen-Activated Protein Kinases
Pneumococcal Infections
Article
I-kappa B Kinase
Mice
Streptococcus pneumoniae
Animals
Humans
Phosphorylation
Casein Kinase II
Cells, Cultured
Signal Transduction
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 351
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.pmid..........5352091ffa5a5646ae1b5017261243d6