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Sung Kyun Moon - One of the best experts on this subject based on the ideXlab platform.
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Synergistic effect of interleukin 1 alpha on nontypeable Haemophilus influenzae-induced up-regulation of human Beta-Defensin 2 in middle ear epithelial cells.
BMC Infectious Diseases, 2006Co-Authors: Sung Kyun Moon, Haa Yung Lee, Huiqi Pan, Tamotsu Takeshita, Raekil Park, Kiweon Cha, Ali Andalibi, David J. LimAbstract:Background We 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.
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synergistic effect of interleukin 1 alpha on nontypeable haemophilus influenzae induced up regulation of human Beta Defensin 2 in middle ear epithelial cells
BMC Infectious Diseases, 2006Co-Authors: Sung Kyun Moon, Haa Yung Lee, Huiqi Pan, Tamotsu Takeshita, Raekil Park, Kiweon Cha, Ali AndalibiAbstract:We 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. The 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. Middle 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. We 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.
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gene regulatory regions required for Beta Defensin 2 up regulation by interleukin 1alpha in the human middle ear epithelial cell line
Korean Journal of Otolaryngology-head and Neck Surgery, 2005Co-Authors: Hyun Jun Kim, Jun Ho Bae, Yunhoon Choung, Keehyun Park, Sung Kyun MoonAbstract:BACKGROUND AND OBJECTIVES: Innate immunity is important in the middle ear because of the lack of immune cells in the region. Among innate immunities Beta-Defensin-2 is known to play an important role in the immune function of the middle ear. But we still do not understand well about the signal transduction pathway and gene regulatory region of Beta-Defensin-2 (hBD-2). MATERIALS AND METHOD: The expression of Beta-Defensin-2 (hBD-2) by IL-1alpha in HMEEC was detected by RT-PCR. The luciferase-expressing vector containing diverse lengths of the hBD-2 5' flanking region made by the progressive unidirectional deletion was transferred to HEEMC (Human Middle Ear Cell). We analyzed the function of 5' flanking region by luciferase activity measured using a luminometer after supplementing corresponding substrates to the cell lysate. RESULTS: hBD-2 was upregulated by IL-1alpha in HMEEC-1. The treatment of IL-1alpha up-regulated the activity of promoter by 7.60+/-1.45 (average+/-standard deviation) folds in 2.7 kpb sized 5' flanking region, 3.81+/-0.78 folds in 1.1 kbp, and 4.00+/-0.73 folds in 500 bp. CONCLUSION: These results indicate there are two effective gene regions that regulate the hBD-2 expression by IL-1alpha between 2.7 kbp and 1.1 kbp, and at 500 bp upstream of the translation starting point of hBD-2 in HMEEC-1
Jürgen Harder - One of the best experts on this subject based on the ideXlab platform.
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Mouse Beta-Defensin-14, an Antimicrobial Ortholog of Human Beta-Defensin-3
Antimicrobial Agents and Chemotherapy, 2008Co-Authors: Kerstin Hinrichsen, Rainer Podschun, Sabine Schubert, Jens M. Schröder, Jürgen Harder, Ehrhardt ProkschAbstract:Searching the database for mouse homologs of the antimicrobial peptide human Beta-Defensin-3 (hBD-3) revealed highest identity (69%) to mouse Beta-Defensin-14 (mBD-14). Recombinant mBD-14 exhibited broad-spectrum, nanomolar microbicidal activity. Treatment of keratinocytes with gamma interferon or transforming growth factor alpha increased mBD-14 gene expression. These data suggest that mBD-14 is the functional ortholog of hBD-3.
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nod2 card15 mediates induction of the antimicrobial peptide human Beta Defensin 2
Journal of Biological Chemistry, 2006Co-Authors: Eske Voss, Jens M. Schröder, Jan Wehkamp, Eduard F Stange, Kai Wehkamp, Jürgen HarderAbstract:Abstract Production of inducible antimicrobial peptides offers a first and rapid defense response of epithelial cells against invading microbes. Human Beta-Defensin-2 (hBD-2) is an antimicrobial peptide induced in various epithelia upon extracellular as well as intracellular bacterial challenge. Nucleotide-binding oligomerization domain protein 2 (NOD2/CARD15) is a cytosolic protein involved in intracellular recognition of microbes by sensing peptidoglycan fragments (e.g. muramyl dipeptide). We used luciferase as a reporter gene for a 2.3-kb hBD-2 promoter to test the hypothesis that NOD2 mediates the induction of hBD-2. Activation of NOD2 in NOD2-overexpressing human embryonic kidney 293 cells through its ligand muramyl dipeptide (MDP) induced hBD-2 expression. In contrast, overexpression of NOD2 containing the 3020insC frame-shift mutation, the most frequent NOD2 variant associated with Crohn disease, resulted in defective induction of hBD-2 through MDP. Luciferase gene reporter analyses and site-directed mutagenesis experiments demonstrated that functional binding sites for NF-κB and AP-1 in the hBD-2 promoter are required for NOD2-mediated induction of hBD-2 through MDP. Moreover, the NF-κB inhibitor Helenalin as well as a super-repressor form of the NF-κB inhibitor IκB strongly inhibited NOD2-mediated hBD-2 promoter activation. Expression of NOD2 was detected in primary keratinocytes, and stimulation of these cells with MDP induced hBD-2 peptide release. In contrast, small interference RNA-mediated down-regulation of NOD2 expression in primary keratinocytes resulted in a defective induction of hBD-2 upon MDP treatment. Together, these data suggest that NOD2 serves as an intracellular pattern recognition receptor to enhance host defense by inducing the production of antimicrobial peptides such as hBD-2.
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Burkholderia Is Highly Resistant to Human Beta-Defensin 3
Antimicrobial Agents and Chemotherapy, 2003Co-Authors: Hany Sahly, Sabine Schubert, Jens M. Schröder, Jürgen Harder, Peter Rautenberg, Uwe Ullmann, Rainer PodschunAbstract:The bactericidal activity of the novel Beta-Defensin hBD-3 against 28 species and 55 strains of gram-positive cocci and gram-negative fermentative and nonfermentative rods was tested. All strains proved to be highly or intermediately susceptible to hBD-3 (minimal bactericidal concentration [MBC], ≤50 μg/ml), except for Burkholderia cepacia, for all 23 tested strains of which MBCs were >100 μg/ml.
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Human Beta-Defensin-2.
The International Journal of Biochemistry & Cell Biology, 1999Co-Authors: Jens M. Schröder, Jürgen HarderAbstract:Human Beta-Defensin-2 (HBD-2) is a cysteine-rich cationic low molecular weight antimicrobial peptide recently discovered in psoriatic lesional skin. It is produced by a number of epithelial cells and exhibits potent antimicrobial activity against Gram-negative bacteria and Candida, but not Gram-positive Staphylococcus aureus. HBD-2 represents the first human Defensin that is produced following stimulation of epithelial cells by contact with microorganisms such as Pseudomonas aeruginosa or cytokines such as TNF-alpha and IL-1 Beta. The HBD-2 gene and protein are locally expressed in keratinocytes associated with inflammatory skin lesions such as psoriasis as well as in the infected lung epithelia of patients with cystic fibrosis. It is intriguing to speculate that HBD-2 is a dynamic component of the local epithelial defense system of the skin and respiratory tract having a role to protect surfaces from infection, and providing a possible reason why skin and lung infections with Gram-negative bacteria are rather rare.
Ali Andalibi - One of the best experts on this subject based on the ideXlab platform.
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Synergistic effect of interleukin 1 alpha on nontypeable Haemophilus influenzae-induced up-regulation of human Beta-Defensin 2 in middle ear epithelial cells.
BMC Infectious Diseases, 2006Co-Authors: Sung Kyun Moon, Haa Yung Lee, Huiqi Pan, Tamotsu Takeshita, Raekil Park, Kiweon Cha, Ali Andalibi, David J. LimAbstract:Background We 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.
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synergistic effect of interleukin 1 alpha on nontypeable haemophilus influenzae induced up regulation of human Beta Defensin 2 in middle ear epithelial cells
BMC Infectious Diseases, 2006Co-Authors: Sung Kyun Moon, Haa Yung Lee, Huiqi Pan, Tamotsu Takeshita, Raekil Park, Kiweon Cha, Ali AndalibiAbstract:We 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. The 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. Middle 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. We 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.
Raekil Park - One of the best experts on this subject based on the ideXlab platform.
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Synergistic effect of interleukin 1 alpha on nontypeable Haemophilus influenzae-induced up-regulation of human Beta-Defensin 2 in middle ear epithelial cells.
BMC Infectious Diseases, 2006Co-Authors: Sung Kyun Moon, Haa Yung Lee, Huiqi Pan, Tamotsu Takeshita, Raekil Park, Kiweon Cha, Ali Andalibi, David J. LimAbstract:Background We 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.
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synergistic effect of interleukin 1 alpha on nontypeable haemophilus influenzae induced up regulation of human Beta Defensin 2 in middle ear epithelial cells
BMC Infectious Diseases, 2006Co-Authors: Sung Kyun Moon, Haa Yung Lee, Huiqi Pan, Tamotsu Takeshita, Raekil Park, Kiweon Cha, Ali AndalibiAbstract:We 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. The 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. Middle 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. We 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.
Tamotsu Takeshita - One of the best experts on this subject based on the ideXlab platform.
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Synergistic effect of interleukin 1 alpha on nontypeable Haemophilus influenzae-induced up-regulation of human Beta-Defensin 2 in middle ear epithelial cells.
BMC Infectious Diseases, 2006Co-Authors: Sung Kyun Moon, Haa Yung Lee, Huiqi Pan, Tamotsu Takeshita, Raekil Park, Kiweon Cha, Ali Andalibi, David J. LimAbstract:Background We 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.
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synergistic effect of interleukin 1 alpha on nontypeable haemophilus influenzae induced up regulation of human Beta Defensin 2 in middle ear epithelial cells
BMC Infectious Diseases, 2006Co-Authors: Sung Kyun Moon, Haa Yung Lee, Huiqi Pan, Tamotsu Takeshita, Raekil Park, Kiweon Cha, Ali AndalibiAbstract:We 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. The 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. Middle 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. We 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.