Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Tumor Microenvironment (Mar 2021)
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a letter
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Research Article Free access | 10.1172/JCI1359

The B1-agonist [des-Arg10]-kallidin activates transcription factor NF-kappaB and induces homologous upregulation of the bradykinin B1-receptor in cultured human lung fibroblasts.

J P Schanstra, E Bataillé, M E Marin Castaño, Y Barascud, C Hirtz, J B Pesquero, C Pecher, F Gauthier, J P Girolami, and J L Bascands

Institut National de la Santé et de la Recherche Médicale (INSERM) U388, Institut Louis BUGNARD, CHU Rangueil, 31052 Toulouse, France.

Find articles by Schanstra, J. in: JCI | PubMed | Google Scholar

Institut National de la Santé et de la Recherche Médicale (INSERM) U388, Institut Louis BUGNARD, CHU Rangueil, 31052 Toulouse, France.

Find articles by Bataillé, E. in: JCI | PubMed | Google Scholar

Institut National de la Santé et de la Recherche Médicale (INSERM) U388, Institut Louis BUGNARD, CHU Rangueil, 31052 Toulouse, France.

Find articles by Marin Castaño, M. in: JCI | PubMed | Google Scholar

Institut National de la Santé et de la Recherche Médicale (INSERM) U388, Institut Louis BUGNARD, CHU Rangueil, 31052 Toulouse, France.

Find articles by Barascud, Y. in: JCI | PubMed | Google Scholar

Institut National de la Santé et de la Recherche Médicale (INSERM) U388, Institut Louis BUGNARD, CHU Rangueil, 31052 Toulouse, France.

Find articles by Hirtz, C. in: JCI | PubMed | Google Scholar

Institut National de la Santé et de la Recherche Médicale (INSERM) U388, Institut Louis BUGNARD, CHU Rangueil, 31052 Toulouse, France.

Find articles by Pesquero, J. in: JCI | PubMed | Google Scholar

Institut National de la Santé et de la Recherche Médicale (INSERM) U388, Institut Louis BUGNARD, CHU Rangueil, 31052 Toulouse, France.

Find articles by Pecher, C. in: JCI | PubMed | Google Scholar

Institut National de la Santé et de la Recherche Médicale (INSERM) U388, Institut Louis BUGNARD, CHU Rangueil, 31052 Toulouse, France.

Find articles by Gauthier, F. in: JCI | PubMed | Google Scholar

Institut National de la Santé et de la Recherche Médicale (INSERM) U388, Institut Louis BUGNARD, CHU Rangueil, 31052 Toulouse, France.

Find articles by Girolami, J. in: JCI | PubMed | Google Scholar

Institut National de la Santé et de la Recherche Médicale (INSERM) U388, Institut Louis BUGNARD, CHU Rangueil, 31052 Toulouse, France.

Find articles by Bascands, J. in: JCI | PubMed | Google Scholar

Published May 15, 1998 - More info

Published in Volume 101, Issue 10 on May 15, 1998
J Clin Invest. 1998;101(10):2080–2091. https://doi.org/10.1172/JCI1359.
© 1998 The American Society for Clinical Investigation
Published May 15, 1998 - Version history
View PDF
Abstract

The bradykinin B1-receptor is strongly upregulated under chronic inflammatory conditions. However, the mechanism and reason are not known. Because a better understanding of the mechanism of the upregulation will help in understanding its potential importance in inflammation, we have studied the molecular mechanism of B1-receptor upregulation in cultured human lung fibroblasts (IMR 90) in response to IL-1beta and the B1-agonist [des-Arg10]-kallidin. We show that treatment of human IMR 90 cells by IL-1beta stimulates the expression of both B1-receptor mRNA and protein. The latter was studied by Western blot analysis using antipeptide antibodies directed against the COOH-terminal part of the human B1-receptor. We furthermore report the novel observation that the B1-receptor is upregulated by its own agonist which was completely blocked by the specific B1-antagonist [des-Arg10-Leu9]-kallidin, indicating an upregulation entirely mediated through cell surface B1-receptors. The increased population of B1-receptors was functionally coupled as exemplified by an enhancement of the B1-agonist induced increase in free cytosolic calcium. Upregulation by the B1-agonist was blocked by a specific protein kinase C inhibitor. B1-agonist-induced upregulation was correlated to the induction of transcription factor nuclear factor kappaB (NF-kappaB) which efficiently bound to the NF-kappaB-like sequence located in the promoter region of the human B1-receptor gene. This correlation was further confirmed by reporter gene assays which showed that this NF-kappaB-like sequence, in the B1-receptor promoter context, could contribute to IL-1beta and DLBK-induced B1-receptor transcription activation, and by the effect of NF-kappaB inhibitor pyrrolidinedithiocarbamate which diminished both B1-receptor upregulation and NF-kappaB activation. NF-kappaB is now recognized as a key inflammatory mediator which is activated by the B1-agonist but which is also involved in B1-receptor upregulation.

Version history
  • Version 1 (May 15, 1998): No description

Article tools

  • View PDF
  • Download citation information
  • Send a letter
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts