PMID- 32182090
OWN - NLM
STAT- MEDLINE
DCOM- 20201013
LR  - 20221117
IS  - 1535-4989 (Electronic)
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 63
IP  - 2
DP  - 2020 Aug
TI  - The Transient Receptor Potential Channel Vanilloid 1 Is Critical in Innate Airway 
      Epithelial Responses to Protease Allergens.
PG  - 198-208
LID - 10.1165/rcmb.2019-0170OC [doi]
AB  - The airway epithelium plays a critical role in innate responses to airborne 
      allergens by secreting IL-1 family cytokines such as IL-1alpha and IL-33 as alarmins 
      that subsequently orchestrate appropriate immune responses. Previous studies 
      revealed that epithelial IL-33 secretion by allergens such as Alternaria 
      alternata or house dust mite involves Ca(2+)-dependent signaling, via initial 
      activation of ATP-stimulated P2YR2 (type 2 purinoceptor) and subsequent 
      activation of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 
      DUOX1. We sought to identify proximal mechanisms by which epithelial cells sense 
      these allergens and here highlight the importance of PAR2 (protease-activated 
      receptor 2) and TRP (transient receptor potential) Ca(2+) channels such as TRPV1 
      (TRP vanilloid 1) in these responses. Combined studies of primary human nasal and 
      mouse tracheal epithelial cells, as well as immortalized human bronchial 
      epithelial cells, indicated the importance of both PAR2 and TRPV1 in IL-33 
      secretion by both Alternaria alternata and house dust mite, based on both 
      pharmacological and genetic approaches. TRPV1 was also critically involved in 
      allergen-induced ATP release, activation of DUOX1, and redox-dependent activation 
      of EGFR (epidermal growth factor receptor). Moreover, genetic deletion of TRPV1 
      dramatically attenuated allergen-induced IL-33 secretion and subsequent type 2 
      responses in mice in vivo. TRPV1 not only contributed to ATP release and P2YR2 
      signaling but also was critical in downstream innate responses to ATP, indicating 
      potentiating effects of P2YR2 on TRPV1 activation. In aggregate, our studies 
      illustrate a complex relationship between various receptor types, including PAR2 
      and P2YR2, in epithelial responses to asthma-relevant airborne allergens and 
      highlight the central importance of TRPV1 in such responses.
FAU - Schiffers, Caspar
AU  - Schiffers C
AUID- ORCID: 0000-0003-2391-1168
AD  - Department of Pathology and Laboratory Medicine, Robert Larner, M.D. College of 
      Medicine, University of Vermont, Burlington, Vermont; and.
AD  - Department of Respiratory Medicine, NUTRIM School for Nutrition, Toxicology, and 
      Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands.
FAU - Hristova, Milena
AU  - Hristova M
AD  - Department of Pathology and Laboratory Medicine, Robert Larner, M.D. College of 
      Medicine, University of Vermont, Burlington, Vermont; and.
FAU - Habibovic, Aida
AU  - Habibovic A
AD  - Department of Pathology and Laboratory Medicine, Robert Larner, M.D. College of 
      Medicine, University of Vermont, Burlington, Vermont; and.
FAU - Dustin, Christopher M
AU  - Dustin CM
AUID- ORCID: 0000-0002-8372-3719
AD  - Department of Pathology and Laboratory Medicine, Robert Larner, M.D. College of 
      Medicine, University of Vermont, Burlington, Vermont; and.
FAU - Danyal, Karamatullah
AU  - Danyal K
AD  - Department of Pathology and Laboratory Medicine, Robert Larner, M.D. College of 
      Medicine, University of Vermont, Burlington, Vermont; and.
FAU - Reynaert, Niki L
AU  - Reynaert NL
AD  - Department of Respiratory Medicine, NUTRIM School for Nutrition, Toxicology, and 
      Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands.
FAU - Wouters, Emiel F M
AU  - Wouters EFM
AD  - Department of Respiratory Medicine, NUTRIM School for Nutrition, Toxicology, and 
      Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands.
FAU - van der Vliet, Albert
AU  - van der Vliet A
AUID- ORCID: 0000-0003-0923-0016
AD  - Department of Pathology and Laboratory Medicine, Robert Larner, M.D. College of 
      Medicine, University of Vermont, Burlington, Vermont; and.
LA  - eng
GR  - R01 HL085646/HL/NHLBI NIH HHS/United States
GR  - R01 HL138708/HL/NHLBI NIH HHS/United States
GR  - T32 HL076122/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Allergens)
RN  - 0 (Receptor, PAR-2)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (TRPV1 protein, human)
RN  - EC 3.4.- (Peptide Hydrolases)
SB  - IM
MH  - Allergens/*immunology
MH  - Animals
MH  - Asthma/immunology
MH  - Bronchi/immunology
MH  - Cells, Cultured
MH  - Epithelial Cells/*immunology
MH  - Epithelium/immunology
MH  - Humans
MH  - Immunity, Innate/*immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Peptide Hydrolases/*immunology
MH  - Pyroglyphidae/immunology
MH  - Receptor, PAR-2/immunology
MH  - Respiratory Mucosa/immunology
MH  - Signal Transduction/immunology
MH  - TRPV Cation Channels/*immunology
PMC - PMC7397771
OTO - NOTNLM
OT  - ATP
OT  - DUOX1
OT  - IL-33
OT  - lung
OT  - type 2 immune responses
EDAT- 2020/03/18 06:00
MHDA- 2020/10/21 06:00
PMCR- 2021/08/01
CRDT- 2020/03/18 06:00
PHST- 2020/03/18 06:00 [pubmed]
PHST- 2020/10/21 06:00 [medline]
PHST- 2020/03/18 06:00 [entrez]
PHST- 2021/08/01 00:00 [pmc-release]
AID - 10.1165/rcmb.2019-0170OC [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2020 Aug;63(2):198-208. doi: 10.1165/rcmb.2019-0170OC.