title: Effect of transient receptor potential vanilloid-1 on cough hypersensitivity induced by particulate matter 2.5.
abstract: OBJECTIVE
  The mechanism of cough hypersensitivity induced by particulate matter 2.5 (PM2.5) remains elusive. The current study was designed to explore the effect of transient receptor potential vanilloid-1 (TRPV1) on cough hypersensitivity in airway and central nervous system.
  
  
  METHODS
  The PM2.5-induced chronic cough model of guinea pig was established by exposure to different doses of PM2.5 for three weeks. After exposure, the animals were microinjected with TRPV1 agonist capsaicine, antagonist capsazepine in the dorsal vagal complex respectively. Cough sensitivity was measured by determining the provocative concentration of citric acid inducing 5 or more coughs (C5). Airway inflammation was detected by hematoxylin eosin (HE) staining and Evans blue fluorescence, and substance P (SP) and TRPV1 expressions in airway were observed by immunohistochemical staining. TRPV1 expressions in the dorsal vagal complex were observed by immunofluorescence. Retrograde tracing by pseudorabies virus-Bartha (PRV-Bartha) was conducted to confirm the regulatory pathway between airway and central nervous system.
  
  
  RESULTS
  PM2.5 induced TRPV1 expressions in both of airway and dorsal vagal complex and airway neurogenic inflammation. Airway vascular permeability increased after being exposed to PM2.5. The expressions of SP in the airway and airway inflammation was increased after microinjecting TRPV1 agonist, and decreased after microinjecting TRPV1 antagonist. PRV infected neurons in medulla oblongata mainly located in the dorsal vagal complex.
  
  
  CONCLUSIONS
  These findings show that TRPV1 in the dorsal vagal complex could promote airway neurogenic inflammation and cough reflex sensitivity through neural pathways of vagal complex-airways, which indicate the therapeutic potential of specific inhibition of TRPV1 for chronic cough induced by PM2.5.
authors.affiliation: Medical School, Southeast University, China.
authors.forename: Haining
authors.initials: H
authors.lastname: Lv
authors.affiliation: Medical School, Southeast University, China.
authors.forename: Jianliang
authors.initials: J
authors.lastname: Yue
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Medical School, Southeast University, China.
authors.forename: Senlin
authors.initials: S
authors.lastname: Chai
authors.affiliation: Medical School, Southeast University, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Cao
authors.affiliation: Medical School, Southeast University, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhan
authors.affiliation: Medical School, Southeast University, China.
authors.forename: Zhenjun
authors.initials: Z
authors.lastname: Ji
authors.affiliation: Key Laboratory of Environmental Medicine and Engineering Ministry of Education, School of Public Health, Southeast University, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pharmacology, Southeast University, China. Electronic address: 13913920819@163.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, China. Electronic address: klai@163.com.
authors.forename: Kefang
authors.initials: K
authors.lastname: Lai
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002211:Capsaicin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002493:Central Nervous System Diseases / Q000235:genetics* / Q000503:physiopathology; D003371:Cough / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology; D006168:Guinea Pigs; D011558:Herpesvirus 1, Suid / Q000235:genetics; D006967:Hypersensitivity / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D052638:Particulate Matter / Q000633:toxicity; D012130:Respiratory Hypersensitivity / Q000235:genetics* / Q000503:physiopathology; D015398:Signal Transduction / Q000235:genetics; D013373:Substance P / Q000096:biosynthesis; D050916:TRPV Cation Channels / Q000187:drug effects / Q000378:metabolism*; D014630:Vagus Nerve / Q000187:drug effects
chemical_list: D052638:Particulate Matter; D050916:TRPV Cation Channels; D013373:Substance P; C071423:capsazepine; D002211:Capsaicin
keywords: Cough reflex sensitivity; Dorsal vagal complex; Neurogenic inflammation; PM2.5; SP; TRPV1