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


OBJECTIVE
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.


CONCLUSIONS
EGFRIs may cause cutaneous adverse effects through selectively perturbing innate immune responses induced by commensal and pathogenic bacteria.
Department of Dermatology, Yamato Takada Municipal Hospital, Nara, Japan; Department of Dermatology, Nara Medical University, Nara, Japan. Electronic address: asadah@naramed-u.ac.jp.
Kio
K
Park
Department of Dermatology, Nara Medical University, Nara, Japan.
Rie
R
Ommori
Department of Dermatology, Nara Medical University, Nara, Japan.
Kyoko
K
Imoto
Department of Dermatology, Nara Medical University, Nara, Japan.
Hideo
H
Asada
D002478:Cells, Cultured; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D015603:Keratinocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D047428:Protein Kinase Inhibitors / Q000633:toxicity*; D011799:Quinazolines / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects; D013211:Staphylococcus aureus / Q000276:immunology / Q000472:pathogenicity; D013212:Staphylococcus epidermidis / Q000276:immunology / Q000472:pathogenicity*; D013997:Time Factors; D023083:beta-Defensins / Q000378:metabolism*
C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D023083:beta-Defensins; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
Erlotinib; Gefitinib; Human β-defensins