Epidermal growth factor receptor inhibitors selectively inhibit the expression of human β-defensins induced by Staphylococci

Abstract

Epidermal growth factor receptor inhibitors (EGFRIs) have developed as one of the potential treatment options for various kinds of cancers. Although a variety of dermatological adverse reactions such as follicular acneiform eruptions is commonly encountered, the mechanism of the reactions remains unclear. We investigated the effects of EGFRIs on the expression of antimicrobial peptides against Staphylococci to study the pathomechanism of cutaneous adverse reactions caused by EGFRIs. We investigated the expressions of human β-defensins 1, 2, and 3 (hBD1, 2, and 3) from Staphylococci-stimulated normal human epidermal keratinocytes (NHEKs) cultured with or without the effects of two EGFRIs, gefitinib and erlotinib. We stimulated NHEKs with the culture supernatants of Staphylococcus aureus (S. aureus) and S. epidermidis and the live Staphylococci. We measured hBDs in the culture supernatants of NHEKs by ELISA. EGFRIs did not suppress the expressions of hBD1 and 3 induced by the supernatants of S. aureus or live S. aureus. In contrast, EGFRIs suppressed the expressions of hBD2 and 3 induced by the supernatants of S. epidermidis and hBD2 induced by live S. aureus. EGFRIs may cause cutaneous adverse effects through selectively perturbing innate immune responses induced by commensal and pathogenic bacteria.