PMID- 34302984
OWN - NLM
STAT- MEDLINE
DCOM- 20211104
LR  - 20220531
IS  - 1522-9629 (Electronic)
IS  - 1094-5539 (Linking)
VI  - 70
DP  - 2021 Oct
TI  - The inflammatory regulation of TRPA1 expression in human A549 lung epithelial 
      cells.
PG  - 102059
LID - S1094-5539(21)00071-7 [pii]
LID - 10.1016/j.pupt.2021.102059 [doi]
AB  - Transient receptor potential ankyrin-1 (TRPA1) is an ion channel mediating pain 
      and cough signals in sensory neurons. We and others have shown that TRPA1 is also 
      expressed in some non-neuronal cells and supports inflammatory responses. To 
      address the pathogenesis and to uncover potential targets for pharmacotherapy in 
      inflammatory lung diseases, we set out to study the expression of TRPA1 in human 
      A549 lung epithelial cells under inflammatory conditions. TRPA1 expression was 
      determined by RT-qPCR and Western blotting at a mRNA and protein level, 
      respectively and its function was studied by Fluo 3-AM intracellular Ca(2+) 
      measurement in A549 lung epithelial cells. TRPA1 promoter activity was assessed 
      by reporter gene assay. TRPA1 expression was very low in A549 cells in the 
      absence of inflammatory stimuli. Tumor necrosis factor-alpha (TNF-alpha) significantly 
      increased TRPA1 expression and a synergy was found between TNF-alpha, interleukin-1beta 
      (IL-1beta) and interferon-gamma (IFN-gamma). Reporter gene experiments indicate that the 
      combination of TNF-alpha and IL-1beta increases TRPA1 promoter activity while the effect 
      of IFN-gamma seems to be non-transcriptional. Interestingly, the glucocorticoid 
      dexamethasone downregulated TRPA1 expression in A549 cells by reducing TRPA1 mRNA 
      stability in a transcription-dependent manner. Furthermore, pharmacological 
      blockade of TRPA1 reduced the production of the pro-inflammatory cytokine IL-8. 
      In conclusion, TRPA1 was found to be expressed and functional in human A549 lung 
      epithelial cells under inflammatory conditions. The anti-inflammatory steroid 
      dexamethasone reduced TRPA1 expression through post-transcriptional mechanisms. 
      The results reveal TRPA1 as a potential mediator and drug target in inflammatory 
      lung conditions.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Luostarinen, Samu
AU  - Luostarinen S
AD  - The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, 
      Tampere University and Tampere University Hospital, Tampere, Finland.
FAU - Hamalainen, Mari
AU  - Hamalainen M
AD  - The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, 
      Tampere University and Tampere University Hospital, Tampere, Finland.
FAU - Hatano, Noriyuki
AU  - Hatano N
AD  - Laboratory of Cellular Pharmacology, School of Pharmacy, Aichi-Gakuin University, 
      Nagoya, Japan.
FAU - Muraki, Katsuhiko
AU  - Muraki K
AD  - Laboratory of Cellular Pharmacology, School of Pharmacy, Aichi-Gakuin University, 
      Nagoya, Japan.
FAU - Moilanen, Eeva
AU  - Moilanen E
AD  - The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, 
      Tampere University and Tampere University Hospital, Tampere, Finland. Electronic 
      address: eeva.moilanen@tuni.fi.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210721
PL  - England
TA  - Pulm Pharmacol Ther
JT  - Pulmonary pharmacology & therapeutics
JID - 9715279
RN  - 0 (Cytokines)
RN  - 0 (TRPA1 Cation Channel)
RN  - 0 (TRPA1 protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - A549 Cells
MH  - *Cytokines
MH  - Epithelial Cells
MH  - Gene Expression
MH  - Humans
MH  - *Lung
MH  - *TRPA1 Cation Channel/genetics
MH  - Tumor Necrosis Factor-alpha
OTO - NOTNLM
OT  - Glucocorticoids
OT  - Inflammation
OT  - Interferon-gamma (IFN-gamma)
OT  - Interleukin-1beta (IL-1beta)
OT  - Transient receptor potential ankyrin 1 (TRPA1) cation channel
OT  - Tumor necrosis factor-alpha (TNF-alpha)
EDAT- 2021/07/25 06:00
MHDA- 2021/11/05 06:00
CRDT- 2021/07/24 20:13
PHST- 2021/03/26 00:00 [received]
PHST- 2021/06/06 00:00 [revised]
PHST- 2021/07/17 00:00 [accepted]
PHST- 2021/07/25 06:00 [pubmed]
PHST- 2021/11/05 06:00 [medline]
PHST- 2021/07/24 20:13 [entrez]
AID - S1094-5539(21)00071-7 [pii]
AID - 10.1016/j.pupt.2021.102059 [doi]
PST - ppublish
SO  - Pulm Pharmacol Ther. 2021 Oct;70:102059. doi: 10.1016/j.pupt.2021.102059. Epub 
      2021 Jul 21.