Staphylococcus aureus stimulates neutrophil targeting chemokine expression in keratinocytes through an autocrine IL-1alpha signaling loop.
Staphylococcus aureus stimulates neutrophil targeting chemokine expression in keratinocytes through an autocrine IL-1alpha signaling loop.
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DOI:
10.1038/jid.2010.37
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发表时间:
2010-07
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影响因子:
--
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中科院分区:
文献类型:
--
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Staphylococcus aureus is a significant human pathogen which can colonize the skin. Neutrophils are well known to be involved in clearance of the bacterium. This study focused on exploring the role human keratinocytes play as first responders to bacterial challenges. IL-1α and IL-1β increased mRNA production and protein secretion of the neutrophil chemotactic CXCL1, CXCL2 and IL-8 in keratinocytes. S. aureus and the bacterial cell wall components lipoteichoic acid (LTA) and peptidoglycan (PGN) induced similar expression profiles in a Toll-like receptor (TLR)-2 dependent manner. Interestingly, the S. aureus induced mRNA levels peaked at later time-points than those induced by IL-1. The S. aureus activated chemokine production was preceded by significant IL-1α and IL-1β secretion. Expression of IL-1α was significantly higher than that of IL-1β. Inhibition of IL-1RI using neutralizing antibodies revealed that S. aureus derived LTA and PGN induced chemokine expression requires IL-1RI engagement. Surprisingly, we further found that chemokine secretion is dependent upon endocrine IL-1α, but not IL-1β, signaling. Our data demonstrate that the innate immune response of keratinocytes is regulated differently than those of other cell types. This may represent a fail-safe system, which protects the host against genetic variation and immune evasion mechanisms developed by pathogens.
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影响因子:
64.8
作者:
Horng, T;Barton, GM;Medzhitov, R
通讯作者:
Medzhitov, R
影响因子:
3.1
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González-Zorn, B;Senna, JPM;Grillot-Courvalin, C
通讯作者:
Grillot-Courvalin, C
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32.4
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Modlin, RL
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Ollert, M
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10.3
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Sasaki, T;Kano, R;Hasegawa, A
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Hasegawa, A