Synergistic effect of interleukin 1 alpha on nontypeable Haemophilus influenzae-induced up-regulation of human beta-defensin 2 in middle ear epithelial cells
| Autor: | Tamotsu Takeshita, David J. Lim, Kiweon Cha, Raekil Park, Huiqi Pan, Sung Kyun Moon, Haa Yung Lee, Ali Andalibi |
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| Rok vydání: | 2006 |
| Předmět: |
Male
beta-Defensins medicine.medical_treatment Clinical Sciences Ear Middle Biology Inbred C57BL Middle Microbiology p38 Mitogen-Activated Protein Kinases lcsh:Infectious and parasitic diseases Cell Line Mice 03 medical and health sciences Paracrine signalling Genetics otorhinolaryngologic diseases medicine 2.1 Biological and endogenous factors Animals Humans lcsh:RC109-216 Aetiology Autocrine signalling 030304 developmental biology 0303 health sciences 030306 microbiology Beta-defensin 2 Interleukin Ear Epithelial Cells Haemophilus influenzae Up-Regulation Cell biology Mice Inbred C57BL Otitis Media Infectious Diseases Beta defensin Cytokine Medical Microbiology Cell culture Immunology Signal transduction Interleukin-1 Signal Transduction Research Article |
| Zdroj: | BMC Infectious Diseases BMC Infectious Diseases, Vol 6, Iss 1, p 12 (2006) BMC infectious diseases, vol 6, iss 1 |
| ISSN: | 1471-2334 |
| DOI: | 10.1186/1471-2334-6-12 |
| Popis: | BackgroundWe recently showed that beta-defensins have antimicrobial activity against nontypeable Haemophilus influenzae (NTHi) and that interleukin 1 alpha (IL-1 alpha) up-regulates the transcription of beta-defensin 2 (DEFB4 according to new nomenclature of the Human Genome Organization) in human middle ear epithelial cells via a Src-dependent Raf-MEK1/2-ERK signaling pathway. Based on these observations, we investigated if human middle ear epithelial cells could release IL-1 alpha upon exposure to a lysate of NTHi and if this cytokine could have a synergistic effect on beta-defensin 2 up-regulation by the bacterial components.MethodsThe studies described herein were carried out using epithelial cell lines as well as a murine model of acute otitis media (OM). Human cytokine macroarray analysis was performed to detect the released cytokines in response to NTHi exposure. Real time quantitative PCR was done to compare the induction of IL-1 alpha or beta-defensin 2 mRNAs and to identify the signaling pathways involved. Direct activation of the beta-defensin 2 promoter was monitored using a beta-defensin 2 promoter-Luciferase construct. An IL-1 alpha blocking antibody was used to demonstrate the direct involvement of this cytokine on DEFB4 induction.ResultsMiddle ear epithelial cells released IL-1 alpha when stimulated by NTHi components and this cytokine acted in an autocrine/paracrine synergistic manner with NTHi to up-regulate beta-defensin 2. This synergistic effect of IL-1 alpha on NTHi-induced beta-defensin 2 up-regulation appeared to be mediated by the p38 MAP kinase pathway.ConclusionWe demonstrate that IL-1 alpha is secreted by middle ear epithelial cells upon exposure to NTHi components and that it can synergistically act with certain of these molecules to up-regulate beta-defensin 2 via the p38 MAP kinase pathway. |
| Databáze: | OpenAIRE |
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