Increased expression of transient receptor potential channels and neurogenic factors associates with cough severity in a guinea pig model

Mengyue Guan,Sun Ying,Yuguang Wang

doi:10.1186/s12890-021-01556-w

Abstract

BackgroundPrevious studies suggest that transient receptor potential (TRP) channels and neurogenic inflammation may be involved in idiopathic pulmonary fibrosis (IPF)-related high cough sensitivity, although the details of mechanism are largely unknown. Here, we aimed to further explore the potential mechanism involved in IPF-related high cough sensitivity to capsaicin challenge in a guinea pig model of pulmonary fibrosis induced by bleomycin.MethodsWestern blotting and real-time quantitative polymerase chain reaction (RT-qPCR) were employed to measure the expression of TRP channel subfamily A, member 1 (TRPA1) and TRP vanilloid 1 (TRPV1), which may be involved in the cough reflex pathway. Immunohistochemical analysis and RT-qPCR were used to detect the expression of neuropeptides substance P (SP), Neurokinin-1 receptor (NK1R), and calcitonin gene-related peptide (CGRP) in lung tissues. Concentrations of nerve growth factor (NGF), SP, neurokinin A (NKA), neurokinin B (NKB), and brain-derived neurotrophic factor (BDNF) in lung tissue homogenates were measured by ELISA.ResultsCough sensitivity to capsaicin was significantly higher in the model group than that of the sham group. RT-qPCR and immunohistochemical analysis showed that the expression of TRPA1 and TRPV1 in the jugular ganglion and nodal ganglion, and SP, NK1R, and CGRP in lung tissue was significantly higher in the model group than the control group. In addition, expression of TRP and neurogenic factors was positively correlated with cough sensitivity of the experimental animals.ConclusionUp-regulated expression of TRPA1 and TRPV1 in the cough reflex pathway and neurogenic inflammation might contribute to the IPF-related high cough sensitivity in guinea pig model.

Highlights

Previous studies suggest that transient receptor potential (TRP) channels and neurogenic inflammation may be involved in idiopathic pulmonary fibrosis (IPF)-related high cough sensitivity, the details of mechanism are largely unknown
Neurogenic inflammation refers to the activation of sensory neurons when they are thermally or chemically stimulated, which leads to the release of substance P (SP), calcitonin gene-related peptide (CGRP), neurokinin A (NKA), and other inflammatory mediators, and to inflammatory reactions such as local tissue edema [8]
We have previously shown that expression of TRPA1 and TRP vanilloid 1 (TRPV1) in the lungs of a guinea pig model of bleomycin-induced pulmonary fibrosis was elevated, which was companied with increased cough sensitivity [15]

Summary

Introduction

Previous studies suggest that transient receptor potential (TRP) channels and neurogenic inflammation may be involved in idiopathic pulmonary fibrosis (IPF)-related high cough sensitivity, the details of mechanism are largely unknown. The pathophysiological mechanism underlying IPF-related cough remains unclear, some studies suggest that it might relate to neurogenic inflammation, transient receptor potential (TRP) channels, and increased cough sensitivity [7]. Neurogenic inflammation refers to the activation of sensory neurons when they are thermally or chemically stimulated, which leads to the release of substance P (SP), calcitonin gene-related peptide (CGRP), neurokinin A (NKA), and other inflammatory mediators, and to inflammatory reactions such as local tissue edema [8]. Neurons release bradykinin, nerve growth factor (NGF), and other inflammatory mediators, which can directly stimulate and activate cough receptors in the airway mucosa, and increase cough sensitivity to normal subliminal stimuli [10]

Objectives

Methods

Results

Discussion

Conclusion