Transient receptor potential ankyrin 1 (TRPA1) positively regulates imiquimod‐induced, psoriasiform dermal inflammation in mice
YanZhou1,2 | DanHan1,2 BoWang4 | ZhenruiShi2 Samuel T. Hwang2 TaylorFollansbee3 | XuesongWu2 | SebastianYu2 | | DanT.Domocos3 | MirelaCarstens3 | EarlCarstens3 |
1Department of Dermatology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
2Department of Dermatology, University of California, Davis, California
3Department of Neurobiology, Physiology and Behavior, University of California, Davis, California
4Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China
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 psori‐ asiform 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 de‐ fects. Additionally, the relative area of epidermal Munro’s microabscesses and mRNA levels of neutrophil inducible chemokines (S100A8, S100A9 and CXCL1) were de‐ creased 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 therapeu‐ tic intervention.
KEYWORDS
imiquimod, inflammation, itch, mice, psoriasis, TRPA1
