Bradykinin B2 receptor expression in the bronchial mucosa of allergic asthmatics: the role of <scp>NF</scp>‐<scp>kB</scp>

Ricciardolo, Fabio Luigi Massimo; Petecchia, Loredana; Sorbello, Valentina; Stefano, Antonino Di; Usai, Cesare; Massaglia, G M; Gnemmi, Isabella; Mognetti, Barbara; Hiemstra, Pieter S.; Sterk, Peter J.; Sabatini, Federica

doi:10.1111/cea.12676

Cited by 14 publications

(13 citation statements)

References 29 publications

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“…The broad spectrum of KKS action are mediated by B1R and B2R, which have been classified as trans-membrane G protein-coupled receptors (GPCR) (da Costa et al 2014). These two receptors are expressed not only on structural cells but on inflammatory cells (Ricciardolo et al 2016). Using double immunofluorescence staining with CK-18 (specifically expressed in renal epithelial cells), the present study showed B1R and B2R were mainly expressed on tubular epithelial cells (Djudjaj et al 2016).…”

Section: Discussionmentioning

confidence: 61%

“…Research has shown B1R itself is able to induce its own expression through the NF-jB pathway, resulting in the elevation of IL-1b and TNFa synthesis (Marcon et al 2013). Another study indicated that B2R expression could be increased in tandem with increased in NF-jB expression (Ricciardolo et al 2016). Thus, it would be important to ascertain if TCE activates the NF-jB signal pathway as part of any induced renal injury and if this could also be mediated by BK receptors.…”

Section: Discussionmentioning

confidence: 99%

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Bradykinin receptor in immune-mediated renal tubular injury in trichloroethylene-sensitized mice: Impact on NF-κB signaling pathway

Yang

Zhang

et al. 2018

Journal of Immunotoxicology

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xing Zhu (2018) Bradykinin receptor in immune-mediated renal tubular injury in trichloroethylene-sensitized mice: Impact on NF-κB signaling pathway, Journal of Immunotoxicology, 15:1, 126-136, ABSTRACT Trichloroethylene (TCE) is known to induce skin disorders and multi-system dysfunction, but the mechanism of this multi-organ injury is not entirely clear. It was shown in a previous study that levels of pivotal end-products of the kallikrein-kinin system (KKS), i.e. bradykinin (BK) and BK receptors B1R/B2R, in the kidneys were increased by TCE exposure. Unfortunately, how BK and its receptors acted in the etiology of the induced renal injury is not clear. Thus, this study explored any correlation between BK receptors and immune renal injury in TCE-sensitized mice by blocking the BK receptors B1R/B2R. BALB/c mice were sensitized (via skin) by TCE, with or without pre-treatment with a B1R or B2R antagonist. Renal lesions, increased expressions of B1R, B2R, Kim-1, Lipocalin-2, and NF-jB p65 subunit on tubular epithelial cells were all observed in TCE-sensitized mice. Serum levels of creatinine (Cr), microglobulin a1 and b2, along with mRNA levels for inflammatory cytokines and NF-jB p65 in kidneys, were all increased by 72 h after a final challenge. Highly selective antagonist pre-treatment blocked B2R and significantly attenuated TCEinduced changes. Blocking B1R or B2R attenuated release of pro-inflammatory cytokines and activation of NF-jB signaling pathway (as reflected in lower up-regulation of pIjB and nuclear NF-jB p65 subunit, and down-regulation of IjB in the kidneys. These results provided evidence that TCE-sensitization caused KKS activation and enhanced the expression of B1R and B2R on tubular epithelial cells. This, in turn, accelerated NF-jB signaling pathway activation and amplified inflammatory cytokine release, which all likely contributed to TCE-induced immune renal injury. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Bradykinin receptor in immune-mediated renal tubular injury in trichloroethylene-sensitized mice: Impact on NF-κB signaling pathway

Yang

Zhang

et al. 2018

Journal of Immunotoxicology

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“…Bradykinin-induced bradykinin B2 receptor expression in human lung fibroblasts is suppressed by corticosteroid treatment (budesonide) (Sabatini et al, 2012), suggesting a potential role for transcription factors in the modulation of bradykinin B2 receptor expression. Bradykinin B2 receptor expression is increased in the bronchial mucosa of mild allergic asthmatics after allergen compared to diluent challenge and, in addition, in bronchial fibroblasts from asthmatics after exposure to the Th2 cytokines IL-4 and IL-13 compared to the untreated fibroblasts (Ricciardolo et al, 2016).…”

mentioning

confidence: 94%

“…The nuclear factor-κB (NF-κB) p65 (Ser 276) inhibitor suppressed bradykinin B2 receptor upregulation induced by bradykinin and IL-4/IL-13 on bronchial fibroblasts in vitro, indicating that bradykinin B2 receptors protein expression is modulated by NF-κB pathway (Ricciardolo et al, 2016).…”

mentioning

confidence: 99%

Bradykinin in asthma: Modulation of airway inflammation and remodelling

Ricciardolo

Folkerts

Folino

et al. 2018

European Journal of Pharmacology

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Bradykinin, a pro-inflammatory molecule, and its related peptides have been studied for their effects on acute reactions in upper and lower airways, where they can be synthesised and metabolized after exposure to different stimuli including allergens and viral infection. Bradykinin B and B receptors are constitutively expressed in the airways on several residential and/or immune cells. Their expression can also be induced by inflammatory mediators, usually associated with eosinophil and neutrophil recruitment, such as IL-4, IL-13, TNF-α, IL-6 and IL-8, via intracellular MAPK and NF-κB signalling. In turn, the latters up-regulate both bradykinin receptors. Bradykinin activates epithelial/endothelial and immune cells, neurons and mesenchymal cells (such as fibroblasts, myofibroblasts and smooth muscle cells), which are implicated in the development of airway chronic inflammation, responsiveness and remodelling (a major feature of severe asthma). This review highlights the role of bradykinin and its receptors in respect to chronic inflammatory response involving eosinophils/neutrophils and to vascular/matrix-related airway remodelling in asthmatic airways. This scenario is especially important for understanding the mechanisms involved in the pathogenesis of eosinophilic and/or neutrophilic asthma and hence their therapeutic approach.

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“…At the inflammation sites, multiple inflammatory cells, including EOS and NE, can generate reactive oxygen species (ROS), which can participate in the development of allergic asthma. ROS promote the activities of pro-inflammatory redox-sensitive nuclear factors, including NF-kB, which can induce various inflammatory genes, including IL-4 and TNF-a, and increase the occurrence of allergic inflammation in asthmatic patients [47]. The OVAinduced levels of inflammatory cytokines were increased compared with the control levels, according to the levels of IL-4 and TNF-a cytokines in BALF analysed using ELISA (Figure 7(B)).…”

Section: Effects Of Ms I On Ova-induced Levels Of Il-4 and Tnf-a Inflmentioning

confidence: 97%

Cyclosporine A/porous quaternized chitosan microspheres as a novel pulmonary drug delivery system

Yang

Wen

Liu

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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N-[(2-Hydroxyl)-propyl-3-trimethyl ammonium] chitosan chloride (HTCC), a hydrosoluble chitosan derivative, has been extensively investigated as a class of drug delivery vehicles because of its unique features. However the studies on HTCC for pulmonary delivery systems have been rarely conducted. This study aimed to design porous microspheres (MS) containing cyclosporine A (CsA) using HTCC as the carrier. The physicochemical properties and biocompatibility of the MS were evaluated. The in vivo efficacy of MS was evaluated in an asthmatic rat model after pulmonary administration. The results showed that porous MS suitable for inhalation could be readily produced by spray drying method. Optimized porous MS in this study exhibited to be biocompatible and safe to use in the lung, and they were effective in suppression of inflammation in the asthmatic rat model. Above all, our results suggested that HTCC porous MS are promising drug carriers for pulmonary drug delivery.

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Bradykinin B2 receptor expression in the bronchial mucosa of allergic asthmatics: the role of NF‐kB

Cited by 14 publications

References 29 publications

Bradykinin receptor in immune-mediated renal tubular injury in trichloroethylene-sensitized mice: Impact on NF-κB signaling pathway

Bradykinin receptor in immune-mediated renal tubular injury in trichloroethylene-sensitized mice: Impact on NF-κB signaling pathway

Bradykinin in asthma: Modulation of airway inflammation and remodelling

Cyclosporine A/porous quaternized chitosan microspheres as a novel pulmonary drug delivery system

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