192 Betacellulin alleviates Th2 cytokine-mediated impairment of skin tight junction barrier through epidermal growth factor receptor and protein kinase C pathway

Betacellulin (BTC) is a peptide ligand that belongs to the epidermal growth factor family, members of which are implicated in skin morphogenesis, homeostasis, repair, and angiogenesis; however, role BTC regulation barrier remains unknown so far. To examine function, we analysed data from two independent Gene Expression Omnibus (GEO) datasets evaluated effects on primary human keratinocytes using real-time PCR, Western blot transepidermal electrical resistance (TER), functional parameter monitor tight junction barrier. We found gene expression was higher lesions patients with atopic dermatitis (AD), this upregulated following biological treatments, suggesting levels might be biomarker for therapy AD. Moreover, stimulation different cytokines, observed mRNA significantly exclusively inhibited by Th2 cytokines such as IL-4 IL-13, play pivotal pathogenesis Furthermore, specific inhibitors receptor protein kinase C abolished BTC-mediated improvement junction-related proteins, including claudin-1 ZO-1 suppressed TER keratinocyte monolayers. Importantly, recovered increased permeability IL-4/IL-13-treated keratinocytes. Together, propose novel potential therapeutic target treatment diseases characterized overproduction dysfunctional