Epidermal growth factor receptor inhibitors selectively inhibit the expressions of human β-defensins induced by Staphylococcus epidermidis

Abstract Background 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 eruptionsis commonly encountered, the mechanism of the reactions remains unclear. Objectives We investigated the effects of EGFRIs on the expression of human β- defensinsagainst staphylococci to study the pathomechanism of cutaneous adverse reactions caused by EGFRIs. Methods We investigated the expressions of human β- defensins1, 2, and 3 (hBD1, 2, and 3) from staphylococci-stimulated normal human epidermal keratinocytes (NHEKs) cultured with or without the effects of two EGFRIs, gefitiniband erlotinib. We stimulated NHEKs with the supernatant of Staphylococcus aureus ( S. aureus ) and S. epidermidis and the live staphylococci. We measured hBDs in the culture supernatants of NHEKs by enzyme-linked immunosorbent assay (ELISA). Results EGFRIs did not suppress the expressions of hBD1 and 3 induced by S. aureus . In contrast, EGFRIs suppressed the expressions of hBD2 and 3 induced by S. epidermidis . Conclusion EGFRIs may cause cutaneous adverse effects through selectively perturbing innate immune responses induced by commensaland pathogenic bacteria.