Human β-defensin-2 induction in Helicobacter pylori-infected gastric mucosal tissues: antimicrobial effect of overexpression

Uehara, Nobuyuki; Yagihashi, Atsuhito; Kondoh, Kei; Tsuji, Naoki; Fujita, Tatsuya; Hamada, Hirofumi; Watanabe, Naoki

doi:10.1099/jmm.0.04985-0

Cited by 50 publications

(31 citation statements)

References 11 publications

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“…Statistical analysis was performed with a one-tailed t test (*, P Ͻ 0.05; **, P Ͻ 0.01). and trachea (3,52,53). The most prominent source of mBD-3 and mBD-14 assembly is likely stimulated nasal mucosa.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-17A (IL-17A) and IL-17F Are Critical for Antimicrobial Peptide Production and Clearance of Staphylococcus aureus Nasal Colonization

et al. 2016

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g Approximately 20% of the population is persistently colonized by Staphylococcus aureus in the nares. Th17-like immune responses mediated by the interleukin-17 (IL-17) family of cytokines and neutrophils are becoming recognized as relevant host defense mechanisms for resolution of S. aureus mucocutaneous infections. Since antimicrobial peptides are regulated by the IL-17 cytokines, we sought to determine the role of IL-17 cytokines in production of antimicrobial peptides in a murine model of S. aureus nasal carriage. We discovered that nasal tissue supernatants have antistaphylococcal activity, and mice deficient in both IL-17A and IL-17F lost the ability to clear S. aureus nasal colonization. IL-17A was found to be sufficient for nasal mBD-3 production ex vivo and was required for CRAMP, mBD-3, and mBD-14 expression in response to S. aureus colonization in vivo. These data were confirmed in a clinical study of nasal secretions in which elevated levels of the human forms of these antimicrobial peptides were found in nasal secretions from healthy human subjects when they were colonized with S. aureus but not in secretions from noncolonized subjects. Together, these data provide evidence for the importance of IL-17A regulation of antimicrobial peptides and IL-17F in the clearance of S. aureus nasal carriage.

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Section: Discussionmentioning

confidence: 99%

Interleukin-17A (IL-17A) and IL-17F Are Critical for Antimicrobial Peptide Production and Clearance of Staphylococcus aureus Nasal Colonization

et al. 2016

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“…hBD-2 represents the first human defensin that is produced by epithelial cells following contact with bacteria, viruses, or cytokines, such as IL-1 and TNF-␣ (2,(17)(18)(19)(20)(21)(22). Although the nature of the regulation is not completely characterized, both the MAPK signal transduction pathway and the NF-B transcription factor have been suggested to be involved (23,24).…”

Section: Il-17 Markedly Up-regulatesmentioning

confidence: 99%

IL-17 Markedly Up-Regulates β-Defensin-2 Expression in Human Airway Epithelium via JAK and NF-κB Signaling Pathways

Kao

Chen

Thai

et al. 2004

The Journal of Immunology

374

314

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Using microarray gene expression analysis, we first observed a profound elevation of human β-defensin-2 (hBD-2) message in IL-17-treated primary human airway epithelial cells. Further comparison of this stimulation with a panel of cytokines (IL-1α, 1β, 2–13, and 15–18; IFN-γ; GM-CSF; and TNF-α) demonstrated that IL-17 was the most potent cytokine to induce hBD-2 message (>75-fold). IL-17-induced stimulation of hBD-2 was time and dose dependent, and this stimulation also occurred at the protein level. Further studies demonstrated that hBD-2 stimulation was attenuated by IL-17R-specific Ab, but not by IL-1R antagonist or the neutralizing anti-IL-6 Ab. This suggests an IL-17R-mediated signaling pathway rather than an IL-17-induced IL-1αβ and/or IL-6 autocrine/paracrine loop. hBD-2 stimulation was sensitive to the inhibition of the JAK pathway, and to the inhibitors that affect NF-κB translocation and the DNA-binding activity of its p65 NF-κB subunit. Transient transfection of airway epithelial cells with an hBD-2 promoter-luciferase reporter gene expression construct demonstrated that IL-17 stimulated promoter-reporter gene activity, suggesting a transcriptional mechanism for hBD-2 induction. These results support an IL-17R-mediated signaling pathway involving JAK and NF-κB in the transcriptional stimulation of hBD-2 gene expression in airway epithelium. Because IL-17 has been identified in a number of airway diseases, especially diseases related to microbial infection, these findings provide a new insight into how IL-17 may play an important link between innate and adaptive immunity, thereby combating infection locally within the airway epithelium.

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“…LL-37 is a cathelicidin with an anti-H. pylori effect [151] , and a recent study demonstrated that cathelicidin limited H. pylori colonization and related gastritis in mouse models [152] . Defensin peptides have also been indicated to impede H. pylori [153] . Human beta defensin 2 and 3 are differentially expressed in gastric mucosa during H. pylori infection [154] .…”

Section: Eradication: Hope Is Coming?mentioning

confidence: 99%

Antibiotic treatment forHelicobacter pylori: Is the end coming?

Kim

Choi

Chung

2015

WJGPT

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Infection with the Gram-negative pathogen Helicobacter pylori (H. pylori ) has been associated with gastroduodenal disease and the importance of H. pylori eradication is underscored by its designation as a group I carcinogen. The standard triple therapy consists of a proton pump inhibitor, amoxicillin and clarithromycin, although many other regimens are used, including quadruple, sequential and concomitant therapy regimens supplemented with metronidazole, clarithromycin and levofloxacin. Despite these efforts, current therapeutic regimens lack efficacy in eradication due to antibiotic resistance, drug compliance and antibiotic degradation by the acidic stomach environment. Core tip: This article reviews the recent literature describing antibiotic resistance and trends in Helicobacter pylori (H. pylori ) treatment. As there is no effective conventional therapy, new treatments are being developed and bismuth quadruple, sequential, concomitant therapies are recommended as a first-line regimen in regions with high levels of clarithromycin resistance. Quinolones have also been used for H. pylori treatment, although the cure rate has gradually reduced with this approach. New therapeutic directions include probiotic supplementation, tailored therapy, novel agents, and nanotechnology.

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Human β-defensin-2 induction in Helicobacter pylori-infected gastric mucosal tissues: antimicrobial effect of overexpression

Cited by 50 publications

References 11 publications

Interleukin-17A (IL-17A) and IL-17F Are Critical for Antimicrobial Peptide Production and Clearance of Staphylococcus aureus Nasal Colonization

Interleukin-17A (IL-17A) and IL-17F Are Critical for Antimicrobial Peptide Production and Clearance of Staphylococcus aureus Nasal Colonization

IL-17 Markedly Up-Regulates β-Defensin-2 Expression in Human Airway Epithelium via JAK and NF-κB Signaling Pathways

Antibiotic treatment forHelicobacter pylori: Is the end coming?

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