Selective induction of antimicrobial peptides from keratinocytes by staphylococcal bacteria

Ommori, Rie; Ouji, Noriko; Mizuno, Fumiko; Kita, Eisuke; Ikada, Yoshito; Asada, Hideo

doi:10.1016/j.micpath.2012.11.005

Cited by 32 publications

(31 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The expression levels of hBDs in the culture supernatants were then evaluated by enzyme-linked immunosorbent assay, as described previously. 6 Consistently with the findings of our previous study, the secreted products of S. aureus and S. epidermidis induced the expression of hBD1 and hBD3 (Fig. 1a, c, e) and hBD2 and hBD3 ( Fig.…”

Section: Research Lettersupporting

confidence: 93%

See 1 more Smart Citation

Epidermal growth factor receptor (EGFR) inhibitory monoclonal antibodies and EGFR tyrosine kinase inhibitors have distinct effects on the keratinocyte innate immune response

et al. 2018

View full text Add to dashboard Cite

Section: Research Lettersupporting

confidence: 93%

“…1b, d, f), respectively. 6 We next examined the effects of EGFR mAbs on the expression of hBD. We found that both EGFR mAbs, cetuximab and panitumumab, suppressed the expression of hBD1 and hBD3 induced by the secreted products of S. aureus (Fig.…”

Section: Research Lettermentioning

confidence: 99%

Epidermal growth factor receptor (EGFR) inhibitory monoclonal antibodies and EGFR tyrosine kinase inhibitors have distinct effects on the keratinocyte innate immune response

et al. 2018

View full text Add to dashboard Cite

“…Keratinocytes serve as the first line of defense against cutaneous pathogens and are able to stimulate an immune response by releasing cytokines, defensins, and antimicrobial cationic peptides, such as LL-37, to fight off pathogens (12). One cytokine that is produced by keratinocytes and has a role in promoting AD is interleukin 18 (IL-18) (13,14).…”

mentioning

confidence: 99%

Staphlyococcus aureus Phenol-Soluble Modulins Stimulate the Release of Proinflammatory Cytokines from Keratinocytes and Are Required for Induction of Skin Inflammation

et al. 2015

View full text Add to dashboard Cite

Staphylococcus aureus is a human commensal that colonizes the skin. While it is normally innocuous, it has strong associations with atopic dermatitis pathogenesis and has become the leading cause of skin and soft tissue infections in the United States. The factors that dictate the role of S. aureus in disease are still being determined. In this work, we utilized primary keratinocyte culture and an epidermal murine colonization model to investigate the role of S. aureus phenol-soluble modulins (PSMs) in proinflammatory cytokine release and inflammation induction. We demonstrated that many species of Staphylococcus are capable of causing release of interleukin 18 (IL-18) from keratinocytes and that S. aureus PSMs are necessary and sufficient to stimulate IL-18 release from keratinocytes independently of caspase 1. Further, after 7 days of epicutaneous exposure to wild-type S. aureus, but not S. aureus ⌬psm, we saw dramatic changes in gross pathology, as well as systemic release of proinflammatory cytokines. This work demonstrates the importance of PSM peptides in S. aureus-mediated inflammatory cytokine release from keratinocytes in vitro and in vivo and further implicates PSMs as important contributors to pathogenesis. Staphylococcus aureus is a human commensal that lives in the nose, skin, and throat in approximately 30% of the human population (1, 2). While S. aureus is usually harmless, it is an opportunistic pathogen that has become a leading cause of nosocomial infections in the United States (3) and can manifest as skin and soft tissue infections, infective endocarditis, osteomyelitis, and sepsis (1). Further, it has a role in exacerbation of atopic dermatitis (AD), a chronic inflammatory disease of the skin that affects up to 20% of children and up to 3% of adults (4, 5). Chronic cutaneous inflammation during AD results in increased production of extracellular matrix components that permit attachment of S. aureus (6). Subsequently, S. aureus promotes AD by stimulating a strong proinflammatory response (7). S. aureus proteins, such as hemolysin ␣ (HLA), staphylococcal protein A (SPA), and lipoteichoic acids (LTA), promote proinflammatory cytokine production from keratinocytes (7-11). However, this stimulation requires the concurrent presence of a surfactant, such as SDS (11).Keratinocytes serve as the first line of defense against cutaneous pathogens and are able to stimulate an immune response by releasing cytokines, defensins, and antimicrobial cationic peptides, such as LL-37, to fight off pathogens (12). One cytokine that is produced by keratinocytes and has a role in promoting AD is interleukin 18 (IL-18) (13,14). IL-18 is a proinflammatory cytokine that is cleaved and activated primarily by caspase 1 (15). Caspase 1 activation occurs following exposure to danger-associated molecular patterns (DAMPs) or pathogen-associated molecular patterns (PAMPs), which stimulate the activation of the inflammasome (16). Caspase 1 activation can also result in the activation of the proinflammatory cytokine IL-1␤ (17)...

show abstract

“…For example, S. epidermidis is able to dampen inflammatory processes after skin wounding [5] and it secretes antimicrobial factors, which restrict the growth of other competing microbes [3,6]. In addition, S. epidermidis directly induces the expression of antimicrobial peptides in keratinocytes [7][8][9] or indirectly via S. epidermidis-spe-F.R. and M.S.…”

Section: Introductionmentioning

confidence: 99%

<b><i>Staphylococcus epidermidis</i></b> Activates Aryl Hydrocarbon Receptor Signaling in Human Keratinocytes: Implications for Cutaneous Defense

Rademacher¹,

Simanski²,

Hesse³

et al. 2018

J Innate Immun

View full text Add to dashboard Cite

Bacterial challenge of keratinocytes with the abundant skin commensal Staphylococcus epidermidis induces distinct innate immune responses, but the underlying molecular mechanisms are still emerging. We report that the aryl hydrocarbon receptor (AhR) was activated in human primary keratinocytes infected with S. epidermidis, leading to induction of the AhR-responsive gene cytochrome P450 1A1 (CYP1A1). In addition, functional AhR was required for S. epidermidis-mediated induction of IL-1β expression in keratinocytes. AhR-dependent gene induction of IL-1β and CYP1A1 was mediated by factor(s) < 2 kDa secreted by S. epidermidis. Blockade of the AhR in a 3D organotypic skin equivalent infected with S. epidermidis attenuated the S. epidermidis-induced CYP1A1 and IL-1β expression. Moreover, S. epidermidis also induced expression of IL-1α and of the antimicrobial peptide human β-defensin-3 in an AhR-dependent manner in a 3D skin equivalent. An increased outgrowth of S. epidermidis on the surface of skin explants treated with a specific AhR inhibitor further indicate a pivotal role of the AhR in mediating an epidermal defense response. Taken together, our data expand the role of the AhR in innate immunity and support a previously unappreciated contribution for the AhR in cutaneous defense.

show abstract

Selective induction of antimicrobial peptides from keratinocytes by staphylococcal bacteria

Cited by 32 publications

References 17 publications

Epidermal growth factor receptor (EGFR) inhibitory monoclonal antibodies and EGFR tyrosine kinase inhibitors have distinct effects on the keratinocyte innate immune response

Epidermal growth factor receptor (EGFR) inhibitory monoclonal antibodies and EGFR tyrosine kinase inhibitors have distinct effects on the keratinocyte innate immune response

Staphlyococcus aureus Phenol-Soluble Modulins Stimulate the Release of Proinflammatory Cytokines from Keratinocytes and Are Required for Induction of Skin Inflammation

<b><i>Staphylococcus epidermidis</i></b> Activates Aryl Hydrocarbon Receptor Signaling in Human Keratinocytes: Implications for Cutaneous Defense

Contact Info

Product

Resources

About