ArticleBMC infectious diseases2008
Induction of beta defensin 2 by NTHi requires TLR2 mediated MyD88 and IRAK-TRAF6-p38MAPK signaling pathway in human middle ear epithelial cells.
Article in BMC infectious diseases, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 56 citations in OpenAlex.
- Effects ofMetabolites · 2025Article
- Establishment of novel immortalized middle ear cell lines as models for otitis media.Laryngoscope investigative otolaryngology · 2023Article
- Increased expression of miR146a dysregulates TLR2-induced HBD2 in airway epithelial cells from patients with COPD.ERJ open research · 2023Article
- Micro RNAs and Circular RNAs in Different Forms of Otitis Media.International journal of molecular sciences · 2023Review
- Innate Immunity in the Middle Ear Mucosa.Frontiers in cellular and infection microbiology · 2021Review
- Genomics of Otitis Media (OM): Molecular Genetics Approaches to Characterize Disease Pathophysiology.Frontiers in genetics · 2020Review
- Saccharomyces cerevisiae β-glucan-induced SBD-1 expression in ovine ruminal epithelial cells is mediated through the TLR-2-MyD88-NF-κB/MAPK pathway.Veterinary research communications · 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
- Induction of Avian β-Defensin 2 Is Possibly Mediated by the p38 MAPK Signal Pathway in Chicken Embryo Fibroblasts After Newcastle Disease Virus Infection.Frontiers in microbiology · 2018Article
- A proteomic characterization of NTHi lysates.International journal of pediatric otorhinolaryngology · 2016Article
- SuperSILAC Quantitative Proteome Profiling of Murine Middle Ear Epithelial Cell Remodeling with NTHi.PloS one · 2016Article
- Article
- Intratympanic Gene Delivery of Antimicrobial Molecules in Otitis Media.Current allergy and asthma reports · 2015Review
- The inflammasome adaptor ASC contributes to multiple innate immune processes in the resolution of otitis media.Innate immunity · 2015Article
- Role of innate immunity in the pathogenesis of otitis media.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2014Review
- Distal NF-kB binding motif functions as an enhancer for nontypeable H. influenzae-induced DEFB4 regulation in epithelial cells.Biochemical and biophysical research communications · 2014Article
- In vitro interaction of Pseudomonas aeruginosa with human middle ear epithelial cells.PloS one · 2014Article
- NOD2/RICK-dependent β-defensin 2 regulation is protective for nontypeable Haemophilus influenzae-induced middle ear infection.PloS one · 2014Article
- Article
- TLR-Dependent Human Mucosal Epithelial Cell Responses to Microbial Pathogens.Frontiers in immunology · 2014Review
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13 authors at 3 institutions in 3 countries.
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Abstract
backgroundAll mucosal epithelia, including those of the tubotympanium, are secreting a variety of antimicrobial innate immune molecules (AIIMs). In our previous study, we showed the bactericidal/bacteriostatic functions of AIIMs against various otitis media pathogens. Among the AIIMs, human beta-defensin 2 is the most potent molecule and is inducible by exposure to inflammatory stimuli such as bacterial components or proinflammatory cytokines. Even though the beta-defensin 2 is an important AIIM, the induction mechanism of this molecule has not been clearly established. We believe that this report is the first attempt to elucidate NTHi induced beta-defensin expression in airway mucosa, which includes the middle ear.
methodsMonoclonal antibody blocking method was employed in monitoring the TLR-dependent NTHi response. Two gene knock down methods - dominant negative (DN) plasmid and small interfering RNA (siRNA) - were employed to detect and confirm the involvement of several key genes in the signaling cascade resulting from the NTHi stimulated beta-defensin 2 expression in human middle ear epithelial cell (HMEEC-1). The student's t-test was used for the statistical analysis of the data.
resultsThe experimental results showed that the major NTHi-specific receptor in HMEEC-1 is the Toll-like receptor 2 (TLR2). Furthermore, recognition of NTHi component(s)/ligand(s) by TLR2, activated the Toll/IL-1 receptor (TIR)-MyD88-IRAK1-TRAF6-MKK3/6-p38 MAPK signal transduction pathway, ultimately leading to the induction of beta-defensin 2.
conclusionThis study found that the induction of beta-defensin 2 is highest in whole cell lysate (WCL) preparations of NTHi, suggesting that the ligand(s) responsible for this up-regulation may be soluble macromolecule(s). We also found that this induction takes place through the TLR2 dependent MyD88-IRAK1-TRAF6-p38 MAPK pathway, with the primary response occurring within the first hour of stimulation. In combination with our previous studies showing that IL-1alpha-induced beta-defensin 2 expression takes place through a MyD88-independent Raf-MEK1/2-ERK MAPK pathway, we found that both signaling cascades act synergistically to up-regulate beta-defensin 2 levels. We propose that this confers an essential evolutionary advantage to the cells in coping with infections and may serve to amplify the innate immune response through paracrine signaling.
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