Suppression of Epidermal Growth Factor Receptor by Erlotinib Attenuates Carvacrol-induced Skin Inflammation

Yujing Wang; Wenjie Huang; Haidong Jia; Qinglian Tang; Qingfei Yin; Yuanyuan Chen; Wumei Wang; Zhengyu Cao

doi:10.2340/actadv.v104.40975

Authors

Yujing Wang Department of TCM Pharmacology, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China
Wenjie Huang Department of TCM Pharmacology, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China
Haidong Jia R&D Center, Shanghai Jahwa United Co., Ltd., Shanghai, China
Qinglian Tang Department of TCM Pharmacology, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China
Qingfei Yin R&D Center, Shanghai Jahwa United Co., Ltd., Shanghai, China
Yuanyuan Chen R&D Center, Shanghai Jahwa United Co., Ltd., Shanghai, China
Wumei Wang Department of Neurosurgery, Renmin Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, China
Zhengyu Cao Department of TCM Pharmacology, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China

DOI:

https://doi.org/10.2340/actadv.v104.40975

Keywords:

Carvacrol, Dermatitis, EGFR, Erlotinib, Keratinocyte

Abstract

Epidermal growth factor receptors (EGFRs) regulate the growth and repair process of epithelia, as well as carcinogenesis. Activation of TRPV3 by carvacrol stimulates skin inflammation and epidermal hyperplasia; the latter can be suppressed by EGFR inhibition. However, whether EGFR signalling is responsible for skin inflammation remains elusive. The current study investigated the effect of erlotinib, an EGFR inhibitor, on skin inflammation in a carvacrol-induced atopic dermatitis mouse model. It was observed that erlotinib significantly attenuated carvacrol-induced overexpression of proinflammatory cytokines and suppressed peripheral blood mononuclear cell recruitment in HaCaT keratinocytes. In addition, it was demonstrated that erlotinib suppressed carvacrol-induced Akt and NF-κB signalling pathways. Furthermore, inhibition of Akt and NF-κB signalling pathways also attenuated the carvacrol-induced keratinocyte proinflammatory response. Finally, it was demonstrated that erlotinib treatment alleviated carvacrol-induced dermatitis. These data demonstrate that erlotinib ameliorates skin inflammation by regulating Akt and NF-κB-mediated keratinocyte proinflammation, suggesting the therapeutic potential of erlotinib, a clinically used EGFR inhibitor, in skin inflammatory diseases.

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