Rie Ommori

Selective induction of antimicrobial peptides from keratinocytes by staphylococcal bacteria.

Staphylococcus aureus (S. aureus) is one of the most clinically important inflammation-inducing pathogens, while Staphylococcus epidermidis (S. epidermidis) is nonpathogenic and hardly causes inflammation on skin. β-defensins, antimicrobial peptides, are secreted from keratinocytes constitutively or upon induction by various microorganisms. However, the difference between S. aureus and S. epidermidis is still unclear in terms of their influences on the production of β-defensins. In this study, we focused on the influences of S. aureus and S. epidermidis on the keratinocyte innate immune response. Pathogenic S. aureus mainly induced human β-defensin (hBD) 1 and hBD3, but not hBD2, and nonpathogenic S. epidermidis mainly induced hBD2 from human keratinocytes. Molecular weight fractions of >10 kDa prepared from S. aureus supernatants induced the production of hBD1 and hBD3. On the other hand, molecular weight fraction of >100 kDa prepared from S. epidermidis supernatants induced the production of hBD2.Furthermore, the secreted products of S. epidermidis used the toll-like receptor (TLR) 2 pathway in the induction of hBD2 production. The secreted products of S. aureus and S. epidermidis differentially induced subtypes of hBD through different receptors, which may be associated with the difference in virulence between these two bacteria.

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. 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.

EGFR inhibitory monoclonal antibodies and EGFR tyrosine kinase inhibitors have distinct effects on the keratinocyte innate immune response

Epidermal growth factor receptor inhibitors (EGFRIs) are a well-established targeted therapy for several cancers. Two categories of EGFRIs are known, EGFR tyrosine kinase inhibitors (EGFR-TKIs) and EGFR monoclonal antibodies (EGFR mAbs). These EGFRIs frequently cause cutaneous adverse effects, such as papulo-pustular eruptions, xerosis and chronic paronychia. This article is protected by copyright. All rights reserved.

Serum thymus and activation-regulated chemokine (TARC) is associated with the severity of drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS)

Drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS) is a severe adverse drug-induced reaction with reactivation of human herpesvirus 6 (HHV-6).1-3 We previously reported that serum thymus and activation-regulated chemokine (TARC) levels were markedly increased in patients with DIHS and suggested TARC as a useful diagnostic marker of DIHS in the early stage.4,5 In this study, we determined whether serum TARC levels correlate with the severity of clinical symptoms and laboratory data in patients with DRESS/DIHS. This article is protected by copyright. All rights reserved.