Role of selective blocking of bradykinin receptor subtypes in attenuating allergic airway inflammation in guinea pigs

El-Kady, Mohamed M.; Girgis, Zarif I.; El-Rasheed, Eman A. Abd; Shaker, Olfat G.; Attallah, Magdy I.; Soliman, Ahmed

doi:10.1016/j.ejphar.2016.06.024

Cited by 5 publications

(3 citation statements)

References 51 publications

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“…900 p,g or 3000 mcg) led to a dose-dependent improvement in pulmonary function tests (PFTs) but no clinically relevant improvement in global symptom score was noted compared to placebo. During the study it has not been shown an acute bronchodilator effect but a gradually (El-Kady et al, 2016). The latter reduced inflammatory cell infiltration, cytokine production and reduced mucus expression (Gurusamy et al, 2016).…”

Section: B1 and B2 Bradykinin Receptor Antagonistsmentioning

confidence: 89%

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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Section: B1 and B2 Bradykinin Receptor Antagonistsmentioning

confidence: 89%

Bradykinin in asthma: Modulation of airway inflammation and remodelling

Ricciardolo

Folkerts

Folino

et al. 2018

European Journal of Pharmacology

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“…We could not test the JAK3 inhibitor on chronic model in the present study. Recent findings have suggested that selective blocking of bradykinin B 1 receptor may be an additional therapeutic strategy for the treatment of allergic airway inflammation (El-Kady et al, 2016 ). In summary, asthmatic models of mice were effectively treated with kinase inhibitor and this could become a closest option for treating allergic asthma.…”

Section: Discussionmentioning

confidence: 99%

Investigation into the Role of PI3K and JAK3 Kinase Inhibitors in Murine Models of Asthma

et al. 2017

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Asthma is a clinical disorder commonly characterized by chronic eosinophilic inflammation, remodeling and hyper responsiveness of the airways. However, the kinases like Phosphoinositide 3 kinase (PI3K) and Janus kinase 3 (JAK3) are involved in mast cell proliferation, activation, recruitment, migration, and prolonged survival of inflammatory cells. The present study was designed to evaluate the in-vivo comparative effects of two kinase inhibitors on airway inflammation and airway remodeling in acute and chronic models of asthma. Mice were sensitized twice intra-peritoneally and then challenged by inhalation with ovalbumin (OVA). They developed an extensive inflammatory response, goblet cell hyperplasia, collagen deposition, airway smooth muscle thickening similar to pathologies observed in human asthma. The effects of PI3K inhibitor (30 mg/kg, p.o), JAK3 inhibitor (30 mg/kg, p.o) and Dexamethasone (0.3 mg/kg) on airway inflammation and remodeling in OVA sensitized/challenged BALB/c mice were evaluated. Twenty-four hours after the final antigen challenge, bronchoalveolar lavage (BAL) and histological examinations were carried out. It was observed that kinase inhibitors significantly reduced airway inflammation as evidenced by the decrease in pro inflammatory cytokines in BALF and lung homogenate and inflammatory cell count in sensitized mice after allergen challenge. Lung histological analysis showed increased infiltration of inflammatory cells, hyperplasia of goblet cells and the collagen deposition, which were significantly reduced with kinase inhibitor. In conclusion, our data suggest that PI3K and JAK3 inhibitors showed promising alternative therapeutic activity in asthma, which might significantly counteract the airway inflammation in patients with allergic asthma.

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“…Some studies have shown that B1R modulates the late phase of lung inflammation 8,9 , while B2R is involved in full-stage airway responses, and mediates NF-kB activation in airway epithelial cells 10 . Identifying the bradykinin receptor subtypes involved at different stages during inflammation of the lung is crucial to improve our understanding of complex pulmonary conditions, including treatment (Tx)-induced lung I/R injury.…”

Section: Introductionmentioning

confidence: 99%

The role of bradykinin in lung ischemia-reperfusion injury in a rat lung transplantation model

Tan

Wang

et al. 2016

Acta Cir. Bras.

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PURPOSE:To investigate the role of bradykinin in a rat lung transplantation (LTx) model and preliminarily discuss the relationship between bradykinin and CD26/DPP-4. METHODS:Rats were randomly divided into four groups: Control (CON), Sham, low potassium dextranglucose (LPD), and AB192 (n=15/group). Orthotopic single LTx was performed in the LPD and AB192 groups. The donor lungs were flush-perfused and preserved with low potassium dextranglucose (LPD) or LPD+CD26/DPP-4 catalytic inhibitor (AB192). LTx was performed after 18 h cold ischemia time and harvested two days post-LTx. Blood gas analysis (PO 2 ), wet/dry weight ratio (W/D), myeloperoxidase activity (MPO), and lipid peroxidation (MDA) were analyzed at 48 hr after transplantation. Immunohistochemical (IHC) analysis was performed in the same sample and validated by Western-Blot. RESULTS:Compared to the LPD group, the AB192 group showed higher PO 2 , lower W/D ratio, and decreased MPO and MDA. IHC studies showed strong bradykinin β2 receptor (B2R) staining in the LPD group, especially in inflammatory cells, alveolar macrophages, and respiratory epithelial cells. Expression of B2R by Western-Blot was significantly different between the AB192 and LPD groups. CONCLUSION:Bradykinin may be a competitive substrate of DPP-4, and decreased bradykinin levels may enhance protective effects against ischemia/reperfusion injury during LTx.

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Role of selective blocking of bradykinin receptor subtypes in attenuating allergic airway inflammation in guinea pigs

Cited by 5 publications

References 51 publications

Bradykinin in asthma: Modulation of airway inflammation and remodelling

Bradykinin in asthma: Modulation of airway inflammation and remodelling

Investigation into the Role of PI3K and JAK3 Kinase Inhibitors in Murine Models of Asthma

The role of bradykinin in lung ischemia-reperfusion injury in a rat lung transplantation model

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