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

Abstract

A B S T R A C TBackground: 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. Objective: To investigate the function of TRPV1 in imiquimod (IMQ)-induced psoriasiform dermatitis (PsD) in mice. Methods: 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. Results: 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. Conclusions: 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.

Immune mediators and therapies for pruritus in atopic dermatitis and psoriasis

“…TRPV1+Na v 1.8+ nociceptors, by interacting with dermal DCs, drive the response of IL-23/IL-17 pathway. 102 We did not see marked changes in behavior signs of pruritus in the TRPV1 knockout mice under the same conditions, suggesting that dermal inflammation and pruritus can be independently mediated in some cases (manuscript submitted). A topical TrkA inhibitor, CT327, has been reported to reduce pruritus in patients with Pso.…”

“…101 Our recent studies showed that TRPV1 knockout mice have significantly reduced epidermal and dermal inflammation and TEWL compared to wildtype mice in the IMQ-mediated model of psoriasiform dermatitis. 102 We did not see marked changes in behavior signs of pruritus in the TRPV1 knockout mice under the same conditions, suggesting that dermal inflammation and pruritus can be independently mediated in some cases (manuscript submitted).…”

TRPV1 in experimental autoimmune prostatitis

“…Although TRPV1 KO mice have been studied in various models of inflammation and mast cell activation, the results are not clear due to conflicting data from different tissues . Thus, we examined whether TRPV1 KO mice or the B6 background strain develop inflammation in the prostate after EAP induction.…”

“…Although TRPV1 KO mice have been studied in various models of inflammation and mast cell activation, the results are not clear due to conflicting data from different tissues. [36][37][38][39][40] Thus, we examined whether TRPV1 KO mice or the B6 background strain develop inflammation in the prostate after EAP induction. Prostate sections stained with H&E and scored for inflammation showed that B6 mice with EAP developed significantly higher levels of inflammation (72%) in the DLP lobes Moreover, we observed abundant leukocyte infiltration in the stroma and near epithelial cells (red arrows) in the DLP lobes from B6 mice with EAP ( Figure 2Ab).…”

Resolvin D3 controls mouse and human nociceptive functions and preclinical progression of psoriasis

“…Previous findings indicate that transient receptor potential (TRP) V1 and TRPV1-expressing nociceptive fibers control cutaneous immune responses after IMQ application. 2,7 Pretreatment with resiniferatoxin, an ultrapotent TRPV1 agonist causing the loss of these fibers, reduced both psoriasiform itch and skin inflammation but at the same time it also abolished the anti-psoriatic effects of RvD3 (see Fig S3). Resolvins are potent inhibitors of TRPV1 and/or TRPA1 4 , and the anti-psoriatic effects of RvD3 may be mediated by its binding to the ALX/FPR2 and the inhibition of these TRP receptors in sensory neurons.…”