Mayara Alves Amorim , Vitor Hélio Souza Oliveira , João B. Calixto , Eunice André
{"title":"Functional interplay between bradykinin receptors and transient receptor potential vanilloid-1 in lipopolysaccharide-induced acute lung injury in mice","authors":"Mayara Alves Amorim , Vitor Hélio Souza Oliveira , João B. Calixto , Eunice André","doi":"10.1016/j.pupt.2025.102384","DOIUrl":null,"url":null,"abstract":"<div><div>In this study, we investigated the functional interplay between bradykinin receptors and the transient receptor potential vanilloid-1 (TRPV1) channel in a mouse model of acute lung injury (ALI) induced by lipopolysaccharide (LPS). Lung and bronchoalveolar lavages were collected at 6 and 24 h after the induction of ALI and evaluated for changes in body weight, inflammatory marker levels, lung injury, and TRPV1 expression. Pretreatments with a TRPV1 antagonist (capsazepine) or B<sub>1</sub> and B<sub>2</sub> receptor antagonists, i.e., DALBK and HOE 140, respectively, were evaluated in this ALI mouse model. The histological score revealed higher levels of lung injury in mice treated with LPS (5 and 10 mg/kg), assessed at both 6 and 24 h, compared to the vehicle-treated group. A loss of body weight was observed within 24 h of ALI induction. Furthermore, collagen deposition, pulmonary oedema, leukocyte influx, and increased cytokine levels were also observed following LPS administration. Pretreatment with capsazepine, DALBK, or HOE 140 not only reversed all inflammatory parameters but also prevented the increased expression of TRPV1 observed in the lungs of mice subjected LPS-induced ALI. Our data suggest that, following LPS-induced ALI, bradykinin activates both B<sub>1</sub> and B<sub>2</sub> receptors associated with the subsequent activation of TRPV1. These findings suggest that bradykinin can activate both B<sub>1</sub> and B<sub>2</sub> receptors, which may contribute functionally to TRPV1 upregulation and activation during LPS-induced ALI. This novel pathway appears to sustain inflammation, offering a new therapeutic target for ALI and ARDS.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"90 ","pages":"Article 102384"},"PeriodicalIF":2.8000,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pulmonary pharmacology & therapeutics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1094553925000410","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
In this study, we investigated the functional interplay between bradykinin receptors and the transient receptor potential vanilloid-1 (TRPV1) channel in a mouse model of acute lung injury (ALI) induced by lipopolysaccharide (LPS). Lung and bronchoalveolar lavages were collected at 6 and 24 h after the induction of ALI and evaluated for changes in body weight, inflammatory marker levels, lung injury, and TRPV1 expression. Pretreatments with a TRPV1 antagonist (capsazepine) or B1 and B2 receptor antagonists, i.e., DALBK and HOE 140, respectively, were evaluated in this ALI mouse model. The histological score revealed higher levels of lung injury in mice treated with LPS (5 and 10 mg/kg), assessed at both 6 and 24 h, compared to the vehicle-treated group. A loss of body weight was observed within 24 h of ALI induction. Furthermore, collagen deposition, pulmonary oedema, leukocyte influx, and increased cytokine levels were also observed following LPS administration. Pretreatment with capsazepine, DALBK, or HOE 140 not only reversed all inflammatory parameters but also prevented the increased expression of TRPV1 observed in the lungs of mice subjected LPS-induced ALI. Our data suggest that, following LPS-induced ALI, bradykinin activates both B1 and B2 receptors associated with the subsequent activation of TRPV1. These findings suggest that bradykinin can activate both B1 and B2 receptors, which may contribute functionally to TRPV1 upregulation and activation during LPS-induced ALI. This novel pathway appears to sustain inflammation, offering a new therapeutic target for ALI and ARDS.
期刊介绍:
Pulmonary Pharmacology and Therapeutics (formerly Pulmonary Pharmacology) is concerned with lung pharmacology from molecular to clinical aspects. The subject matter encompasses the major diseases of the lung including asthma, cystic fibrosis, pulmonary circulation, ARDS, carcinoma, bronchitis, emphysema and drug delivery. Laboratory and clinical research on man and animals will be considered including studies related to chemotherapy of cancer, tuberculosis and infection. In addition to original research papers the journal will include review articles and book reviews.
Research Areas Include:
• All major diseases of the lung
• Physiology
• Pathology
• Drug delivery
• Metabolism
• Pulmonary Toxicology.