Synergistic activation of NF-{kappa}B by nontypeable H. influenzae and S. pneumoniae is mediated by CK2, IKK{beta}-I{kappa}B{alpha}, and p38 MAPK

Journal Article · Fri Dec 15 04:00:00 EST 2006 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2006.10.052· OSTI ID:20857915

Kweon, Soo-Mi ^[1]; Wang, Beinan ^[2]; Rixter, Davida ^[3]; Lim, Jae Hyang; Koga, Tomoaki; Ishinaga, Hajime ^[1]; Chen, L -F ^[4]; Jono, Hirofumi; Haidong, Xu ^[1]; Li, J -D ^[1]

---

1. Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642 (United States)
2. Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455 (United States)
3. Gonda Department of Cell and Molecular Biology, House Ear Institute, University of Southern California, Los Angeles, CA 90057 (United States)
4. Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801 (United States)

In review of the past studies on NF-{kappa}B regulation, most of them have focused on investigating how NF-{kappa}B 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-{kappa}B and the subsequent inflammatory response in a synergistic manner. Here, we show that NTHi and S. pneumoniae synergistically induce NF-{kappa}B-dependent inflammatory response via activation of multiple signaling pathways in vitro and in vivo. The classical IKK{beta}-I{kappa}B{alpha} and p38 MAPK pathways are involved in synergistic activation of NF-{kappa}B via two distinct mechanisms, p65 nuclear translocation-dependent and -independent mechanisms. Moreover, casein kinase 2 (CK2) is involved in synergistic induction of NF-{kappa}B 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-{kappa}B-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.

• OSTI ID: 20857915
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 351; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CASEIN
HAEMOPHILUS
IN VITRO
IN VIVO
INFLAMMATION
PHOSPHORYLATION
RESPIRATORY SYSTEM DISEASES
REVIEWS
STREPTOCOCCUS
TRANSLOCATION