Upregulated levels of human β‐defensins in patients with seasonal allergic rhinitis after allergen‐specific immunotherapy treatment

Bogefors, Jesper; Kvarnhammar, Anne Månsson; Cardell, Lars-Olaf

doi:10.1002/alr.21127

Cited by 9 publications

(10 citation statements)

References 26 publications

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“…HDM mice challenged with methacholine demonstrated methacholine dose-dependent increases in Penh levels, which were significantly reduced in SIT mice compared to HDM mice (Figure 2A , p<0.001). Having confirmed that induced IgG4 seems to suppress IgE levels, which was associated with treatment efficacy in allergic patients receiving subcutaneous immunotherapy [ 16 ]. SIT selectively removed long-lived IgE antibodies on mast cells [ 17 ].…”

Section: Resultsmentioning

confidence: 97%

Allergen specific immunotherapy enhanced defense against bacteria via TGF-β1-induced CYP27B1 in asthma

et al. 2017

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Allergen specific immunotherapy (SIT) is the only specific treatment of allergic diseases at present. How SIT impacts pulmonary innate immunity against bacteria currently remains unclear. In this study, dust mite extracts (HDM)-sensitized mice were immunized with a subcutaneous injection of HDM. These mice were then challenged with an intranasal administration of HDM. After the last challenge, mice were infected with an intranasal instillation with P. aeruginosa (P.a). We measured the score of tissue inflammation, the expression of cathelicidin-related antimicrobial peptide (CRAMP) and 25-Hydroxyvitamin D-1Alpha-hydroxylase (CYP27B1) in lung. We analyzed the effect of TGF-β1 on CRAMP and CYP27B1 in airway cells (16HBE), and investigate the role of TGF-β1-induced CYP27B1 in defense against bacteria in16HBE cell. We found that SIT attenuates HDM-induced airway inflammation and airway responsiveness (AHR), which is involved in the increased levels of HDM-specific IgG2a, IL-10, TGF-β1, IFN-γ, CRAMP and CYP27B1. SIT ameliorates pulmonary infectious inflammation associated with an improving defense of HDM-challenged mice against P. aeruginosa. Meanwhile, TGF-β1 significantly increased the expression of CYP27B1 in a dose-dependent manner. TGF-β1 did not increase the levels of CRAMP in airway epithelial cells. Furthermore, 25-dihydroxyvitamin D3 (25VD3) is required for TGF-β1-induced CRAMP in airway epithelial cells. CRAMP was significantly increased in TGF-β1/25VD3-treated 16HBE cells. These findings illustrated that TGF-β1 is a major player against bacterial infections in SIT models via induction of CYP27B1 rather than CRAMP. Collectively, these findings highlight a role for SIT enhancing host defense against bacteria depending on TGF-β1-induced CYP27B1in asthma.

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Section: Resultsmentioning

confidence: 97%

Allergen specific immunotherapy enhanced defense against bacteria via TGF-β1-induced CYP27B1 in asthma

et al. 2017

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“…In the study conducted by Bogefors et al (8), it was found that BD-1 and BD-3 expression in tonsillary tissues was lower in patients with AR compared with healthy controls. In another study, it was shown that BD-1 and BD-3 expressions significantly increased compared with the pre-treatment period in nasal biopsy samples of patients with AR after allergen-specific immunotherapy was completed (9). Similarly, Choi et al (18) found that BD-2 mRNA expression and protein levels in tonsillary and adenoid tissues of patients with AR were significantly lower compared with healthy controls.…”

Section: Discussionmentioning

confidence: 93%

“…Although the molecular mechanism of this has not been fully elucidated at the present time, it is thought that Th2 cytokines reduce defensin expression by leading to inhibition in the tumor necrosis factor (TNF)-α/ nuclear factor (NF)-κB system by way of signal transducer and activator of transcription (STAT) 6 activation (23,26). One of the reasons underlying the fact that immunotherapy increases BD-2 expression in the nasal mucosa may be the inhibition of Th2-type immune response by immunotherapy (9,27).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, they have been shown to have a regulatory function in many physiologic processes including antitumoral immunity, cytokine release, chemotaxis, histamine production, inflammation, and wound healing (7). Although there are a few studies conducted with adults in the literature, no studies have investigated the roles of defensins in the pathogenesis of AR in childhood (8,9). In this study, we aimed to investigate the levels of β-defensin 2 (BD-2), which is AMP synthesized in the respiratory tract of pediatric patients with AR.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of nasal fluid β-defensin 2 levels in children with allergic rhinitis

et al. 2017

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Aim: Knowledge about the role of the innate immune system in the pathogenesis of allergic diseases has been expanding in recent years. Defensins are antimicrobial peptides that are components of the innate immune system. Defensins have strong efficacy against bacterial, viral, and fungal infections. Moreover, they have regulatory functions in many physiologic processes such as antitumoral immunity, chemotaxis, inflammation, and wound healing. In this study, we aimed to investigate β-defensin 2 levels in the nasal fluids of children with allergic rhinitis. Material and Methods:Study and control groups consisted of 28 patients with newly diagnosed allergic rhinitis who were not taking any medication, and 23 healthy children. Skin prick tests were performed on patients with allergic rhinitis and disease severity was assessed using the total symptom score. Nasal fluid samples were obtained using a modified polyurethane sponge absorption method from patients and control subjects. Nasal fluid β-defensin 2 levels were determined using an enzyme-linked immunosorbent assay (ELISA). Results:The median value of nasal fluid β-defensin 2 levels were 173.8 pg/mL (interquartile range; 54.8-205.9 pg/mL) in allergic rhinitis group and 241.6 pg/mL (163.5-315.2 pg/mL) in the control group. There was a statistically significant difference between the two groups (p=0.01). Moreover, nasal fluid β-defensin 2 levels showed a significant negative correlation with total symptom scores (rho= -0.78, p<0.001). Conclusions:Children with allergic rhinitis have reduced nasal fluid β-defensin 2 levels compared with controls, and β-defensin 2 levels were negatively correlated with disease severity. A more definite understanding of the roles of defensins and other antimicrobial peptides in allergic inflammation can open up new horizons in the management and treatment of these common diseases. (Turk Pediatri Ars 2017; 52: 79-84)

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“…Previous investigations of a group of AMPs, the human beta defensins (HBDs) have been performed in the upper respiratory tract. In these studies, a link between allergic status and expression of HBDs was revealed (Bogefors et al ., ). Similar connections were observed in other AMPs, such as S100A7 (also known as psoriasin; Bryborn et al ., ).…”

Section: Introductionmentioning

confidence: 97%

LEAP-2, LL-37 and RNase7 in tonsillar tissue: downregulated expression in seasonal allergic rhinitis

et al. 2014

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In the upper airway, the production of antimicrobial peptides (AMPs) protects against bacteria, viruses and fungi. Previous investigations have revealed downregulated expression of AMPs in different manifestations of allergic disease. In this study, we examined the expression of LL-37, Ribonuclease7 (RNase7) and Liver-expressed antimicrobial peptide 2 (LEAP-2) in tonsillar tissue and studied a possible relation to seasonal allergic rhinitis (SAR). Tonsils, obtained from patients with SAR and nonallergic controls, were examined for the occurrence of LL-37, RNase7 and LEAP-2 with real-time RT-PCR and immunohistochemistry. Tonsillar mononuclear cells were cultured in presence or absence of LEAP-2 or LL-37 and analyzed for cytokine levels using ELISA. mRNA and protein for LL-37, RNase 7 and LEAP-2 were found in all tonsils. Immunohistochemistry revealed prominent staining for LL-37 and RNase7 in the tonsillar epithelium, whereas a moderate staining was seen with LEAP-2. Real-time RT-PCR showed a downregulation of RNase7 and LEAP-2 in the allergic as compared to the nonallergic group. Mononuclear cells cultured in presence of LEAP-2 or LL-37 demonstrated reduced levels of IL-10. The present study demonstrates the presence and function of LEAP-2, LL-37 and RNase7 in tonsils. Moreover, a downregulation of LEAP-2 and RNase7 is seen in SAR patients, indicating that allergic individuals may be more susceptible to respiratory tract infections due to an impaired antimicrobial defense.

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Upregulated levels of human β‐defensins in patients with seasonal allergic rhinitis after allergen‐specific immunotherapy treatment

Abstract: The present study demonstrates an upregulation of HBD1 and HBD2 in SAR patients after completion of ASIT. This may reflect the importance of an intact innate immune response as part of our defense against infections among allergic individuals.

Cited by 9 publications

References 26 publications

Allergen specific immunotherapy enhanced defense against bacteria via TGF-β1-induced CYP27B1 in asthma

Allergen specific immunotherapy enhanced defense against bacteria via TGF-β1-induced CYP27B1 in asthma

Evaluation of nasal fluid β-defensin 2 levels in children with allergic rhinitis

LEAP-2, LL-37 and RNase7 in tonsillar tissue: downregulated expression in seasonal allergic rhinitis

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