EGFR阻害薬は表皮ブドウ球菌によるβディフェンシンの発現を選択的に抑制する

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 eruptions is commonly encountered, the mechanism of the reactions remains unclear. OBJECTIVES: We investigated the effects of EGFRIs on the expression of human β-defensins against staphylococci to study the pathomechanism of cutaneous adverse reactions caused by EGFRIs. METHODS: 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 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 commensal and pathogenic bacteria.博士（医学）・乙第1423号・平成30年11月30日Copyright © 2014 Elsevier Ireland Ltd. All rights reserved