Contribution of sensory nerves to LPS-induced hyperresponsiveness of human isolated bronchi

Luigino Calzetta, Livio Luongo, Mario Cazzola, Clive Page, Paola Rogliani, Francesco Facciolo, Sabatino Maione, Annalisa Capuano, Barbara Rinaldi, Maria Gabriella Matera

Research output: Contribution to journalArticlepeer-review


Aims Bacterial lipopolysaccharide (LPS) can induce bronchial hyperresponsiveness (BHR), but the underlying mechanisms remain to be determined. Here, the possible contribution of sensory nerves to LPS-induced BHR was examined in human isolated bronchi to pharmacologically identify the mechanisms underlying this phenomenon. Main methods Human isolated bronchial tone was induced by electrical field stimulation (EFS). The responses of airways to LPS, with or without capsaicin desensitization or thiorphan treatment were studied and the transient receptor potential vanilloid type 1 (TRPV1) expression was assessed. We performed similar experiments in the presence of a TRPV1 or a neurokinin (NK) 2 receptor antagonist using SB366791 and GR159897, respectively. Key findings LPS increased (≃ 2.3-fold, P <0.001) the contraction induced by EFS, compared to control tissues. Acute administration of capsaicin enhanced (≃ 2.3-fold, P <0.001) the EFS-mediated contraction, but did not potentiate the effect of LPS. Thiorphan increased (≃ 1.3-fold, P <0.05) the contractile response of LPS treated tissues and, at lower frequencies, it enhanced (≃ 1.7-fold, P <0.001) the capsaicin-induced contraction. In capsaicin-desensitized bronchi, LPS did not modify (P > 0.05) the EFS contractile response, nor after treatment with thiorphan. Capsaicin desensitization reduced (≃ 0.4-fold, P <0.001) the LPS-induced BHR. SB366791 and GR159897 prevented the LPS-induced BHR and the release of NKA. LPS increased (+ 85.3 ± 9.5%, P <0.01) the surface membrane expression of TRPV1 in parasympathetic ganglia. Significance Our results demonstrate the involvement of capsaicin-sensitive sensory nerves and neutral endopeptidases in LPS-induced BHR of the human bronchi, associated with an upregulation of TRPV1 and release of NKA.

Original languageEnglish
Pages (from-to)44-50
Number of pages7
JournalLife Sciences
Publication statusPublished - Jun 15 2015


  • BHR
  • Human isolated bronchi
  • LPS
  • NK<inf>2</inf> receptor
  • NKA
  • Sensory nerves
  • TRPV1

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)


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