An important role of α-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by Staphylococcus aureus.

Skin barrier disruption and dermal inflammation are key phenotypes of atopic dermatitis (AD). Staphylococcus aureus secretes extracellular vesicles (EVs), which are involved in AD pathogenesis. Here, we evaluated the role of EVs-associated α-hemolysin derived from S. aureus in AD pathogenesis. α-hem...

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Main Authors: Sung-Wook Hong, Eun-Byul Choi, Taek-Ki Min, Ji-Hyun Kim, Min-Hye Kim, Seong Gyu Jeon, Byung-Jae Lee, Yong Song Gho, Young-Koo Jee, Bok-Yang Pyun, Yoon-Keun Kim
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24992681/?tool=EBI
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author Sung-Wook Hong
Eun-Byul Choi
Taek-Ki Min
Ji-Hyun Kim
Min-Hye Kim
Seong Gyu Jeon
Byung-Jae Lee
Yong Song Gho
Young-Koo Jee
Bok-Yang Pyun
Yoon-Keun Kim
author_facet Sung-Wook Hong
Eun-Byul Choi
Taek-Ki Min
Ji-Hyun Kim
Min-Hye Kim
Seong Gyu Jeon
Byung-Jae Lee
Yong Song Gho
Young-Koo Jee
Bok-Yang Pyun
Yoon-Keun Kim
author_sort Sung-Wook Hong
collection DOAJ
description Skin barrier disruption and dermal inflammation are key phenotypes of atopic dermatitis (AD). Staphylococcus aureus secretes extracellular vesicles (EVs), which are involved in AD pathogenesis. Here, we evaluated the role of EVs-associated α-hemolysin derived from S. aureus in AD pathogenesis. α-hemolysin production from S. aureus was detected using western blot analyses. The cytotoxic activity of α-hemolysin on HaCaT keratinocytes was evaluated by measuring cell viability after treating cells with soluble and EVs-associated α-hemolysin. To determine the type of cell death, HaCaT keratinocytes were stained with annexin V and 7-AAD. The in vivo effects of α-hemolysin were evaluated by application of soluble and EV-associated α-hemolysin on the mouse skin. The present study showed that increased α-hemolysin was produced by S. aureus colonized on AD patients compared to healthy subjects. α-hemolysin production was also related to AD severity. In addition, EV-associated α-hemolysin was more cytotoxic to HaCaT keratinocytes than soluble α-hemolysin, and α-hemolysin-negative EVs did not induce keratinocyte death. EV-associated α-hemolysin induced necrosis, but soluble α-hemolysin induced apoptosis of keratinocytes. In vivo, skin barrier disruption and epidermal hyperplasia were induced by soluble and EV-associated α-hemolysin. However, AD-like dermal inflammation was only caused by EV-associated α-hemolysin. Moreover, neither skin barrier disruption nor AD-like skin inflammation was induced by α-hemolysin-negative EVs. Taken together, α-Hemolysin secreted from S. aureus, particularly the EV-associated form, induces both skin barrier disruption and AD-like skin inflammation, suggesting that EV-associated α-hemolysin is a novel diagnostic and therapeutic target for the control of AD.
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spelling doaj.art-6d35659879274668ab94424b16bcfc522022-12-21T17:44:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10049910.1371/journal.pone.0100499An important role of α-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by Staphylococcus aureus.Sung-Wook HongEun-Byul ChoiTaek-Ki MinJi-Hyun KimMin-Hye KimSeong Gyu JeonByung-Jae LeeYong Song GhoYoung-Koo JeeBok-Yang PyunYoon-Keun KimSkin barrier disruption and dermal inflammation are key phenotypes of atopic dermatitis (AD). Staphylococcus aureus secretes extracellular vesicles (EVs), which are involved in AD pathogenesis. Here, we evaluated the role of EVs-associated α-hemolysin derived from S. aureus in AD pathogenesis. α-hemolysin production from S. aureus was detected using western blot analyses. The cytotoxic activity of α-hemolysin on HaCaT keratinocytes was evaluated by measuring cell viability after treating cells with soluble and EVs-associated α-hemolysin. To determine the type of cell death, HaCaT keratinocytes were stained with annexin V and 7-AAD. The in vivo effects of α-hemolysin were evaluated by application of soluble and EV-associated α-hemolysin on the mouse skin. The present study showed that increased α-hemolysin was produced by S. aureus colonized on AD patients compared to healthy subjects. α-hemolysin production was also related to AD severity. In addition, EV-associated α-hemolysin was more cytotoxic to HaCaT keratinocytes than soluble α-hemolysin, and α-hemolysin-negative EVs did not induce keratinocyte death. EV-associated α-hemolysin induced necrosis, but soluble α-hemolysin induced apoptosis of keratinocytes. In vivo, skin barrier disruption and epidermal hyperplasia were induced by soluble and EV-associated α-hemolysin. However, AD-like dermal inflammation was only caused by EV-associated α-hemolysin. Moreover, neither skin barrier disruption nor AD-like skin inflammation was induced by α-hemolysin-negative EVs. Taken together, α-Hemolysin secreted from S. aureus, particularly the EV-associated form, induces both skin barrier disruption and AD-like skin inflammation, suggesting that EV-associated α-hemolysin is a novel diagnostic and therapeutic target for the control of AD.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24992681/?tool=EBI
spellingShingle Sung-Wook Hong
Eun-Byul Choi
Taek-Ki Min
Ji-Hyun Kim
Min-Hye Kim
Seong Gyu Jeon
Byung-Jae Lee
Yong Song Gho
Young-Koo Jee
Bok-Yang Pyun
Yoon-Keun Kim
An important role of α-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by Staphylococcus aureus.
PLoS ONE
title An important role of α-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by Staphylococcus aureus.
title_full An important role of α-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by Staphylococcus aureus.
title_fullStr An important role of α-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by Staphylococcus aureus.
title_full_unstemmed An important role of α-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by Staphylococcus aureus.
title_short An important role of α-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by Staphylococcus aureus.
title_sort important role of α hemolysin in extracellular vesicles on the development of atopic dermatitis induced by staphylococcus aureus
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24992681/?tool=EBI
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