You are here: Home Published Research Transforming growth factor-beta -Smad signaling pathway cooperates with NF-kappa B to mediate nontypeable Haemophilus influenzae-induced MUC2 mucin transcription.

Hirofumi Jono, Tsuyoshi Shuto, Haidong Xu, Hirofumi Kai, David J Lim, James R Gum, Young S Kim, Shoji Yamaoka, Xin-Hua Feng, and Jian-Dong Li (2002)

Transforming growth factor-beta -Smad signaling pathway cooperates with NF-kappa B to mediate nontypeable Haemophilus influenzae-induced MUC2 mucin transcription.

The Journal of biological chemistry, 277(47):45547–45557.

Transforming growth factor-beta (TGF-beta) and related factors are multifunctional cytokines that regulate diverse cellular processes, including proliferation, differentiation, apoptosis, and immune response. The involvement of TGF-beta receptor-mediated signaling in bacteria-induced up-regulation of mucin, a primary innate defensive response for mammalian airways, however, still remains unknown. Here, we report that the bacterium nontypeable Haemophilus influenzae (NTHi), an important human respiratory pathogen, utilizes the TGF-beta-Smad signaling pathway together with the TLR2-MyD88-TAK1-NIK-IKKbeta/gamma-IkappaBalpha pathway to mediate NF-kappaB-dependent MUC2 mucin transcription. The NTHi-induced TGF-beta receptor Type II phosphorylation occurred at as early as 5 min. Pretreatment of NTHi with TGF-beta neutralization antibody reduced up-regulation of MUC2 transcription. Moreover, functional cooperation of NF-kappaB p65/p50 with Smad3/4 appears to positively mediate NF-kappaB-dependent MUC2 transcription. These data are the first to demonstrate the involvement of TGF-beta receptor-mediated signaling in bacteria-induced up-regulation of mucin transcription, bring insights into the novel role of TGF-beta signaling in bacterial pathogenesis, and may lead to new therapeutic intervention of NTHi infections.

Adaptor Proteins, Signal Transducing, Antigens, Differentiation, Autocrine Communication, Cell Line, DNA-Binding Proteins, Drosophila Proteins, Gene Expression Regulation, Genes, Bacterial, Genes, Reporter, Haemophilus influenzae, Humans, I-kappa B Kinase, I-kappa B Proteins, Membrane Glycoproteins, Models, Biological, Mucin-2, Mucins, Myeloid Differentiation Factor 88, NF-kappa B, Promoter Regions, Genetic, Protein-Serine-Threonine Kinases, Receptors, Cell Surface, Receptors, Immunologic, Receptors, Steroid, Receptors, Thyroid Hormone, Serotyping, Signal Transduction, Smad Proteins, Toll-Like Receptor 2, Toll-Like Receptors, Trans-Activators, Transcription, Genetic, Transforming Growth Factor beta
Adaptor Proteins, Signal Transducing, Antigens, Differentiation, Autocrine Communication, Cell Line, DNA-Binding Proteins, Drosophila Proteins, Gene Expression Regulation, Genes, Bacterial, Genes, Reporter, Haemophilus influenzae, Humans, I-kappa B Kinase, I-kappa B Proteins, Membrane Glycoproteins, Models, Biological, Mucin-2, Mucins, Myeloid Differentiation Factor 88, NF-kappa B, Promoter Regions, Genetic, Protein-Serine-Threonine Kinases, Receptors, Cell Surface, Receptors, Immunologic, Receptors, Steroid, Receptors, Thyroid Hormone, Serotyping, Signal Transduction, Smad Proteins, Toll-Like Receptor 2, Toll-Like Receptors, Trans-Activators, Transcription, Genetic, Transforming Growth Factor beta
 
Document Actions