TRPV1 mediates inflammation and hyperplasia in imiquimod (IMQ)-induced psoriasiform dermatitis (PsD) in mice

• Published in: Journal of dermatological science Vol. 92; no. 3; pp. 264 - 271
• Main Authors: Zhou, Yan, Follansbee, Taylor, Wu, Xuesong, Han, Dan, Yu, Sebastian, Domocos, Dan T., Shi, Zhenrui, Carstens, Mirela, Carstens, Earl, Hwang, Samuel T.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2018
• Subjects: Animals; Cytokines - immunology; Cytokines - metabolism; Disease Models, Animal; Epidermis - immunology; Epidermis - pathology; Female; Humans; Hyperplasia - immunology; Hyperplasia - pathology; Imiquimod - immunology; Itch; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Pain neuroinflammation; Psoriasis; Psoriasis - immunology; Psoriasis - pathology; TRPV Cation Channels - genetics; TRPV Cation Channels - metabolism; Water Loss, Insensible; Psoriasis; Pain neuroinflammation; Itch
• ISSN: 0923-1811; 1873-569X
• DOI: 10.1016/j.jdermsci.2018.11.009

•Imiquimod-induced psoriasiform dermatitis in TRPV1 KO mice is markedly diminished.•TRPV1 plays a role in epidermal barrier dysfunction of psoriasiform dermatitis.•TRPV1 regulates accumulation of inflammatory cells in psoriasiform dermatitis.•Inflammatory cytokine genes are mediated by TRPV1 in psoriasiform dermatitis.•TRPV1 is a potential target for treatment in psoriasiform dermatitis. Transient Receptor Potential Vanilloid 1 (TRPV1) is known to mediate itch and neurogenic inflammation, but the role of TRPV1 in psoriasiform dermal inflammation is poorly understood. To investigate the function of TRPV1 in imiquimod (IMQ)-induced psoriasiform dermatitis (PsD) in mice. Following daily treatment of topical IMQ cream for consecutive 5 days in C57BL/6 wide-type (WT) and TRPV1 gene knockout (KO) mice, we assessed the psoriasis severity index (PSI) scores, transepidermal water loss (TEWL), dermal inflammatory infiltrates, as well as gene expression levels for psoriasis related genes in mouse skin lesions. Compared with WT mice, the clinical and TEWL scores, the extent of skin hyperplasia, the area of Munro microabscesses (MM) and angiogenesis of psoriasis were all significantly decreased in TRPV1 KO mice triggered with IMQ, suggesting a reduction in skin inflammation and barrier defects. In addition, the infiltration of CD45+ leukocytes, mast cells as well as CD3+ T cells was all reduced in the IMQ-treated skin of TRPV1 KO mice. Quantitative Real-time PCR (RT-qPCR) revealed that expression levels of IL-1β, IL-6, IL-23, S100A8 were decreased while IL-10 was increased in TRPV1 KO mice. In summary, key markers of psoriatic inflammation and epidermal hyperplasia are reduced in TRPV1 KO mice, indicating the involvement of TRPV1 in the psoriasiform inflammation and suggesting its potential as a therapeutic target.