Epidermal Growth Factor Relieves Inflammatory Signals in<i>Staphylococcus aureus</i>-Treated Human Epidermal Keratinocytes and Atopic Dermatitis-Like Skin Lesions in Nc/Nga Mice

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a defective immunologic barrier, which is aggravated by <i>Staphylococcus aureus (S. aureus)</i>. Epidermal growth factor (EGF) suppresses inflammation and EGF receptor inhibitors increased <i>S. aureus</i> colonization. Thus, we investigated the potential roles of EGF in AD, which is often aggravated by <i>S. aureus</i>. We determined how EGF affects the expression of inflammatory cytokines and antimicrobial peptides (AMPs) in human epidermal keratinocytes (HEKs) treated with heat-inactivated <i>S. aureus</i> (HKSA) <i>in vitro</i> and 2,4-dinitrochlorobenzene-induced AD-like skin lesions in Nc/Nga mice. HKSA increased IL-6 and NF<i>κ</i>B expression; EGF treatment had the opposite effect. EGF increased human <i>β</i> defensin-2 expression in HEKs and murine <i>β</i> defensin-3 in mice. In mice, both EGF and pimecrolimus groups showed less erythema with significantly reduced inflammation and decreased expression of thymic stromal lymphopoietin. EGF relieved <i>S. aureus</i>-induced inflammation and AD-like skin lesions in Nc/Nga mice. Therefore, EGF could be a potential topical treatment for AD.