Propionibacterium acnes Activates the NLRP3 Inflammasome in Human Sebocytes

Propionibacterium acne and sebaceous glands are considered to have an important role in the development of acne. Although information regarding the activation of innate immunity by P. acnes in the sebaceous gland is limited, different P. acnes phylotypes and a higher prevalence of follicular P. acne...

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Veröffentlicht in:Journal of investigative dermatology 2014-11, Vol.134 (11), p.2747-2756
Hauptverfasser: Li, Zheng Jun, Choi, Dae Kyoung, Sohn, Kyung Cheol, Seo, Min Seok, Lee, Hae Eul, Lee, Young, Seo, Young Joon, Lee, Young Ho, Shi, Ge, Zouboulis, Christos C., Kim, Chang Deok, Lee, Jeung Hoon, Im, Myung
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container_end_page 2756
container_issue 11
container_start_page 2747
container_title Journal of investigative dermatology
container_volume 134
creator Li, Zheng Jun
Choi, Dae Kyoung
Sohn, Kyung Cheol
Seo, Min Seok
Lee, Hae Eul
Lee, Young
Seo, Young Joon
Lee, Young Ho
Shi, Ge
Zouboulis, Christos C.
Kim, Chang Deok
Lee, Jeung Hoon
Im, Myung
description Propionibacterium acne and sebaceous glands are considered to have an important role in the development of acne. Although information regarding the activation of innate immunity by P. acnes in the sebaceous gland is limited, different P. acnes phylotypes and a higher prevalence of follicular P. acnes macrocolonies/biofilms in sebaceous follicles of skin biopsies from acne compared with control skin and occasionally single P. acnes clusters in single sebaceous glands have been detected. In this study, we investigated whether P. acnes activates the inflammasome in human sebaceous glands in vivo and in vitro. We found that IL-1β expression was upregulated in sebaceous glands of acne lesions. After stimulation of human sebocytes with P. acnes, the activation of caspase-1 and secretion of IL-1β were enhanced significantly. Moreover, knocking down the expression of NLRP3 abolished P. acnes-induced IL-1β production in sebocytes. The activation of the NLRP3 inflammasome by P. acnes was dependent on protease activity and reactive oxygen species generation. Finally, we found that NALP3-deficient mice display an impaired inflammatory response to P. acnes. These results suggest that human sebocytes are important immunocompetent cells that induce the NLRP3 inflammasome, and that P. acnes-induced IL-1β activation in sebaceous glands may have a role in combating skin infections and in acne pathogenesis.
doi_str_mv 10.1038/jid.2014.221
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Although information regarding the activation of innate immunity by P. acnes in the sebaceous gland is limited, different P. acnes phylotypes and a higher prevalence of follicular P. acnes macrocolonies/biofilms in sebaceous follicles of skin biopsies from acne compared with control skin and occasionally single P. acnes clusters in single sebaceous glands have been detected. In this study, we investigated whether P. acnes activates the inflammasome in human sebaceous glands in vivo and in vitro. We found that IL-1β expression was upregulated in sebaceous glands of acne lesions. After stimulation of human sebocytes with P. acnes, the activation of caspase-1 and secretion of IL-1β were enhanced significantly. Moreover, knocking down the expression of NLRP3 abolished P. acnes-induced IL-1β production in sebocytes. The activation of the NLRP3 inflammasome by P. acnes was dependent on protease activity and reactive oxygen species generation. Finally, we found that NALP3-deficient mice display an impaired inflammatory response to P. acnes. 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subjects Acne Vulgaris - immunology
Acne Vulgaris - microbiology
Adult
Animals
Carrier Proteins - metabolism
Caspase 1 - metabolism
Cells, Cultured
Female
Humans
Inflammation
Interleukin-1beta - metabolism
Male
Mice
Mice, Inbred C57BL
NLR Family, Pyrin Domain-Containing 3 Protein
Peptide Hydrolases - metabolism
Propionibacterium acnes
Propionibacterium acnes - metabolism
Reactive Oxygen Species
Sebaceous Glands - cytology
Sebaceous Glands - microbiology
Skin - metabolism
Skin - microbiology
Up-Regulation
Young Adult
title Propionibacterium acnes Activates the NLRP3 Inflammasome in Human Sebocytes
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