Transient receptor potential ankyrin 1 (TRPA1) positively regulates imiquimod-induced, psoriasiform dermal inflammation in mice

Yan Zhou, Dan Han, Taylor Follansbee, Xuesong Wu, Sebastian Yu, Bo Wang, Zhenrui Shi, Dan T. Domocos, Mirela Carstens, Earl Carstens, Samuel T Hwang

Research output: Contribution to journalArticle

Abstract

Transient receptor potential ankyrin 1 (TRPA1), a membrane protein ion channel, is known to mediate itch and pain in skin. The function of TRPA1, however, in psoriasiform dermatitis (PsD) is uncertain. Herein, we found that expression of TRPA1 is highly up-regulated in human psoriatic lesional skin. To study the role of TRPA1 in PsD, we assessed Psoriasis Severity Index (PSI) scores, transepidermal water loss (TEWL), skin thickness and pathology, and examined dermal inflammatory infiltrates, Th17-related genes and itch-related genes in c57BL/6 as wild-type (WT) and TRPA1 gene knockout (KO) mice following daily application of topical IMQ cream for 5 days. Compared with WT mice, clinical scores, skin thickness change and TEWL scores were similar on day 3, but were significantly decreased on day 5 in IMQ-treated TRPA1 KO mice (vs WT mice), suggesting reduced inflammation and skin barrier defects. Additionally, the relative area of epidermal Munro's microabscesses and mRNA levels of neutrophil inducible chemokines (S100A8, S100A9 and CXCL1) were decreased in the treated skin of TRPA1 KO mice, suggesting that neutrophil recruitment was impaired in the KO mice. Furthermore, mast cells, CD31+ blood vascular cells, CD45+ leukocytes and CD3+ T cells were all reduced in the treated skin of TRPA1 KO mice. Lastly, mRNA expression levels of IL-1β, IL-6, IL-23, IL-17A, IL-17F and IL-22 were decreased in TRPA1 KO mice. In summary, these results suggest a key role for TRPA1 in psoriasiform inflammation and raising its potential as a target for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)4819-4828
Number of pages10
JournalJournal of Cellular and Molecular Medicine
Volume23
Issue number7
DOIs
StatePublished - Jul 1 2019

Fingerprint

imiquimod
Ankyrins
Inflammation
Skin
Knockout Mice
Interleukin-17
Dermatitis
Interleukin-23
Messenger RNA
Gene Knockout Techniques
Neutrophil Infiltration
Water
Interleukin-1
Ion Channels
Chemokines
Psoriasis
Mast Cells

Keywords

  • imiquimod
  • inflammation
  • itch
  • mice
  • psoriasis
  • TRPA1

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

Cite this

Transient receptor potential ankyrin 1 (TRPA1) positively regulates imiquimod-induced, psoriasiform dermal inflammation in mice. / Zhou, Yan; Han, Dan; Follansbee, Taylor; Wu, Xuesong; Yu, Sebastian; Wang, Bo; Shi, Zhenrui; Domocos, Dan T.; Carstens, Mirela; Carstens, Earl; Hwang, Samuel T.

In: Journal of Cellular and Molecular Medicine, Vol. 23, No. 7, 01.07.2019, p. 4819-4828.

Research output: Contribution to journalArticle

Zhou, Y, Han, D, Follansbee, T, Wu, X, Yu, S, Wang, B, Shi, Z, Domocos, DT, Carstens, M, Carstens, E & Hwang, ST 2019, 'Transient receptor potential ankyrin 1 (TRPA1) positively regulates imiquimod-induced, psoriasiform dermal inflammation in mice', Journal of Cellular and Molecular Medicine, vol. 23, no. 7, pp. 4819-4828. https://doi.org/10.1111/jcmm.14392
Zhou, Yan ; Han, Dan ; Follansbee, Taylor ; Wu, Xuesong ; Yu, Sebastian ; Wang, Bo ; Shi, Zhenrui ; Domocos, Dan T. ; Carstens, Mirela ; Carstens, Earl ; Hwang, Samuel T. / Transient receptor potential ankyrin 1 (TRPA1) positively regulates imiquimod-induced, psoriasiform dermal inflammation in mice. In: Journal of Cellular and Molecular Medicine. 2019 ; Vol. 23, No. 7. pp. 4819-4828.
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abstract = "Transient receptor potential ankyrin 1 (TRPA1), a membrane protein ion channel, is known to mediate itch and pain in skin. The function of TRPA1, however, in psoriasiform dermatitis (PsD) is uncertain. Herein, we found that expression of TRPA1 is highly up-regulated in human psoriatic lesional skin. To study the role of TRPA1 in PsD, we assessed Psoriasis Severity Index (PSI) scores, transepidermal water loss (TEWL), skin thickness and pathology, and examined dermal inflammatory infiltrates, Th17-related genes and itch-related genes in c57BL/6 as wild-type (WT) and TRPA1 gene knockout (KO) mice following daily application of topical IMQ cream for 5 days. Compared with WT mice, clinical scores, skin thickness change and TEWL scores were similar on day 3, but were significantly decreased on day 5 in IMQ-treated TRPA1 KO mice (vs WT mice), suggesting reduced inflammation and skin barrier defects. Additionally, the relative area of epidermal Munro's microabscesses and mRNA levels of neutrophil inducible chemokines (S100A8, S100A9 and CXCL1) were decreased in the treated skin of TRPA1 KO mice, suggesting that neutrophil recruitment was impaired in the KO mice. Furthermore, mast cells, CD31+ blood vascular cells, CD45+ leukocytes and CD3+ T cells were all reduced in the treated skin of TRPA1 KO mice. Lastly, mRNA expression levels of IL-1β, IL-6, IL-23, IL-17A, IL-17F and IL-22 were decreased in TRPA1 KO mice. In summary, these results suggest a key role for TRPA1 in psoriasiform inflammation and raising its potential as a target for therapeutic intervention.",
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AU - Shi, Zhenrui

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