PMID- 33805042
OWN - NLM
STAT- MEDLINE
DCOM- 20210609
LR  - 20210609
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 7
DP  - 2021 Mar 24
TI  - Transient Receptor Potential Ankyrin 1 (TRPA1)-An Inflammation-Induced Factor in 
      Human HaCaT Keratinocytes.
LID - 10.3390/ijms22073322 [doi]
LID - 3322
AB  - Transient receptor potential ankyrin 1 (TRPA1) is an ion channel mainly studied 
      in sensory neurons where it mediates itch, pain and neurogenic inflammation. 
      Recently, some nonneuronal cells have also been shown to express TRPA1 to support 
      inflammatory responses. To address the role of TRPA1 in skin inflammation, we 
      aimed to investigate TRPA1 expression in keratinocytes. HaCaT cells (a model of 
      human keratinocytes) and skin biopses from wild-type and TRPA1 deficient mice 
      were used in the studies. TRPA1 expression in nonstimulated keratinocytes was 
      very low but significantly inducible by the proinflammatory cytokine tumor 
      necrosis factor (TNF) in an nuclear factor kappa B (NF-kappaB), and mitogen-activated 
      protein (MAP) kinase (p38 and c-Jun N-terminal kinase, JNK)-dependent manner. 
      Interestingly, drugs widely used to treat skin inflammation, the calcineurin 
      inhibitors tacrolimus and cyclosporine and the glucocorticoid dexamethasone, 
      significantly decreased TRPA1 expression. Furthermore, pharmacological inhibition 
      and genetic deletion of TRPA1 reduced the synthesis of TNF-induced monocyte 
      chemoattractant protein 1 (MCP-1) in keratinocytes and mouse skin biopsies. In 
      conclusion, these findings point to an inflammatory role for TRPA1 in 
      keratinocytes and present TRPA1 as a potential drug target in inflammatory skin 
      diseases.
FAU - Luostarinen, Samu
AU  - Luostarinen S
AD  - The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, 
      Tampere University and Tampere University Hospital, 33014 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, 33014 Tampere, Finland.
FAU - Moilanen, Eeva
AU  - Moilanen E
AUID- ORCID: 0000-0002-8577-0316
AD  - The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, 
      Tampere University and Tampere University Hospital, 33014 Tampere, Finland.
LA  - eng
GR  - Academy of Finland/
GR  - Research Foundation 300 of Rheumatic Diseases, Finland/
GR  - Tampere Tuberculosis Foundation/
GR  - Competitive State Research Financing of the Expert Responsibility Area of Tampere 
      University Hospital/
PT  - Journal Article
DEP - 20210324
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (CCL2 protein, human)
RN  - 0 (Calcineurin Inhibitors)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Glucocorticoids)
RN  - 0 (NF-kappa B)
RN  - 0 (TRPA1 Cation Channel)
RN  - 0 (TRPA1 protein, human)
RN  - 0 (Trpa1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Biopsy
MH  - Calcineurin Inhibitors/pharmacology
MH  - Chemokine CCL2/metabolism
MH  - Female
MH  - Glucocorticoids/metabolism
MH  - HEK293 Cells
MH  - HaCaT Cells
MH  - Humans
MH  - Inflammation
MH  - Keratinocytes/*metabolism
MH  - MAP Kinase Signaling System
MH  - Mice
MH  - Mice, Knockout
MH  - NF-kappa B/metabolism
MH  - Skin/*metabolism/pathology
MH  - TRPA1 Cation Channel/*metabolism
PMC - PMC8037497
OTO - NOTNLM
OT  - calcineurin inhibitors
OT  - glucocorticoids
OT  - inflammation
OT  - transient receptor potential ankyrin 1 (TRPA1) cation channel
OT  - tumor necrosis factor (TNF)
COIS- The authors declare no conflict of interest.
EDAT- 2021/04/04 06:00
MHDA- 2021/06/10 06:00
PMCR- 2021/03/24
CRDT- 2021/04/03 01:19
PHST- 2021/02/08 00:00 [received]
PHST- 2021/03/10 00:00 [revised]
PHST- 2021/03/17 00:00 [accepted]
PHST- 2021/04/03 01:19 [entrez]
PHST- 2021/04/04 06:00 [pubmed]
PHST- 2021/06/10 06:00 [medline]
PHST- 2021/03/24 00:00 [pmc-release]
AID - ijms22073322 [pii]
AID - ijms-22-03322 [pii]
AID - 10.3390/ijms22073322 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Mar 24;22(7):3322. doi: 10.3390/ijms22073322.