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Abstract
Airway sensory nerves are known to express several receptors and channels that are activated by exogenous and endogenous mediators that cause coughing. Toll-like receptor (TLR) s are expressed in nociceptive neurons and play an important role in neuroinflammation. However, there have been very few studies of TLR expression in lung-derived sensory neurons or their relevance to respiratory symptoms such as cough. We used the bleomycin-induced pulmonary fibrosis model to investigate the change in TLR expression in pulmonary neurons and the association of TLRs with transient receptor potential (TRP) channels in pulmonary neurons. After 2 weeks of bleomycin or saline administration, pulmonary fibrosis changes were confirmed using tissue staining and the SIRCOL collagen assay. TLRs (TLR 1–9) and TRP channel expression was analyzed using single cell reverse transcription polymerase chain reaction (RT-PCR) in isolated sensory neurons from the nodose/jugular ganglion and the dorsal root ganglion (DRG). Pulmonary sensory neurons expressed TLR2 and TLR5. In the bleomycin-induced pulmonary fibrosis model, TLR2 expression was detected in 29.5% (18/61) and 26.9% (21/78) of pulmonary nodose/jugular neurons and DRG neurons, respectively. TLR5 was also detected in 55.7% (34/61) and 42.3% (33/78) of pulmonary nodose/jugular neurons and DRG neurons, respectively, in the bleomycin-induced pulmonary fibrosis model. TLR5 was expressed in 63.4% of TRPV1 positive cells and 43.4% of TRPM8 positive cells. In conclusion, TLR2 and TLR5 expression is enhanced, especially in vagal neurons, in the bleomycin-induced fibrosis model group when compared to the saline treated control group. Co-expression of TLR5 and TRP channels in pulmonary sensory neurons was also observed. This work sheds new light on the role of TLRs in the control and manifestation of clinical symptoms, such as cough. To understand the role of TLRs in pulmonary sensory nerves, further study will be required.
Highlights
To identify the expression and role of toll-like receptor (TLR) in pulmonary sensory neurons, we investigated the expression of TLRs and transient receptor potential (TRP) channels in isolated rat pulmonary sensory neurons using single cell reverse transcription polymerase chain reaction (RT-PCR) in the bleomycin-induced fibrosis murine model
This study observed that pulmonary sensory neurons express the TLR varieties, TLR2 and TLR5
The expression of TLR2 and TLR5 was enhanced especially in vagal neurons in the bleomycin-induced fibrosis model group compared to the saline-treated control group
Summary
The sensory nerves that innervate the respiratory tract are known to express several receptors and channels that are activated by exogenous and endogenous mediators in respiratory disease. The ion channels like transient receptor potential (TRP) channels on vagal sensory afferents are involved in initiating cough [2]. Some experts proposed that cough, pain and itch had shared mechanisms of neuro-immune interaction. In these different conditions, ion channels such as TRPA1 and Nav1.8, and TLRs were implicated in peripheral sensitization and neurogenic inflammation [11]. Investigation of TLRs in pulmonary sensory neurons or the association between TLRs, TRP channels and respiratory symptoms, such as cough, have not been studied sufficiently
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