334 TRPV3 modulates mast cells biological activity via stimulating IL33 release in atopic dermatitis

Transient receptor potential vanilloid 3 subtype (TRPV3) plays an important role in pruritus. From our previous work, chronic pruritus dominantly attenuated TRPV3 knockout mice (TRPV3 KO). We found functional coupled with protease-activated 2 (PAR2) keratinocytes inducing TSLP releasing atopic dermatitis (AD). With bioinformatics investigation, we that mast cells of KO infiltrated less the dermis than those wild type (WT) controls MC903 treatment. Mast cell activation markers were significantly downregulated deficiency WT group. At same time, expression cytokine interleukin 33 (IL-33) was decreased mice. Pharmacological inhibition and siRNA interference assay confirmed IL-33 is a downstream after PAR2-TRPV3 pathway primary keratinocytesin vitro. activated calmodulin-dependent protein kinase, which further caused phosphorylation MARK kinase family nuclear transcription factor activator protein-1 to promote synthesis IL-33. by from AD immune microenvironment. Chemotaxis mouse bone marrow-derived (BMMCs) IL33 dose-dependent manner. In addition, also regulated neuropeptides DRGs. This work expanded understanding TRP channels regulating itching cytokines neuro-immunity network. More importantly, findings provide new theoretical basis for inhibitors treat itch inflammation dermatitis.