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Toll‐like Receptor 7 on Airway Nerves Causes Bronchodilation
Author(s) -
Drake Matthew Georgenson,
Proskocil Becky J,
Lebold Katherine,
Blum Emily,
Fryer Allison,
Jacoby David
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1263.7
Subject(s) - bronchodilation , agonist , methacholine , airway , nitric oxide , medicine , anesthesia , lung , receptor , respiratory disease , bronchodilator , asthma
BACKGROUND Toll‐like receptor 7 (TLR7) detects viral single‐stranded RNA and triggers an innate immune response. We found that TLR7 agonists also induce a rapid and potent bronchodilation in the lung. OBJECTIVE To evaluate TLR7 expression and function in the lung. METHODS TLR7 expression was evaluated in lungs of Hartley guinea pigs and human trachea and primary bronchi (from deceased donors) using immunohistochemistry and RT‐PCR. TLR7's effect on bronchoconstriction was assessed using an organ bath system. Airways were contracted with methacholine (3 μM) and treated with TLR7 agonist R837 (10–300 μM). Some airways were pre‐treated with nitric oxide synthase inhibitor (L‐NMMA) or TLR7 antagonist IRS661. To differentiate the role of specific TLR7‐expressing airway nerve subtypes, some airways were cultured with or without attached sensory nerve ganglia for 48 hours prior to physiology experiments. RESULTS Airway parasympathetic nerves, and sensory nerves that originate in in the nodose, jugular, dorsal root and esophageal ganglia all express TLR7. TLR7 agonist rapidly dilated pre‐contracted human and guinea pig airways. TLR7‐mediated bronchodilation was blocked by TLR7 antagonist and by inhibition of nitric oxide production. Bronchodilation was unchanged in airways whose sensory nerves had undergone degeneration, suggesting parasympathetic nerves alone are sufficient for TLR7‐induced bronchodilation. CONCLUSIONS TLR7 is expressed by airway parasympathetic and sensory nerves. TLR7 mediates a rapid and potent bronchodilation. These data suggest that TLR7 is a potential bronchodilatory therapeutic target in humans. Support or Funding Information Funding Source: This project was supported by NIH grants HL121254, HL124165, HL113023, AR061567.