title: Propionibacterium acnes activates the NLRP3 inflammasome in human sebocytes.
abstract: 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.
authors.affiliation: Department of Dermatology, College of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Zheng Jun
authors.initials: ZJ
authors.lastname: Li
authors.affiliation: Department of Dermatology, College of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Dae Kyoung
authors.initials: DK
authors.lastname: Choi
authors.affiliation: Department of Dermatology, College of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Kyung Cheol
authors.initials: KC
authors.lastname: Sohn
authors.affiliation: Department of Dermatology, College of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Min Seok
authors.initials: MS
authors.lastname: Seo
authors.affiliation: Department of Dermatology, College of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Hae Eul
authors.initials: HE
authors.lastname: Lee
authors.affiliation: Department of Dermatology, College of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Dermatology, College of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Young Joon
authors.initials: YJ
authors.lastname: Seo
authors.affiliation: Department of Anatomy, College of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Dermatology, The Affiliated hospital of Guangdong Medical College, Zhanjiang, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Shi
authors.affiliation: Department of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Dessau, Germany.
authors.forename: Christos C
authors.initials: CC
authors.lastname: Zouboulis
authors.affiliation: Department of Dermatology, College of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Chang Deok
authors.initials: CD
authors.lastname: Kim
authors.affiliation: Department of Dermatology, College of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Jeung Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Dermatology, College of Medicine, Chungnam National University, Daejeon, Korea. Electronic address: im1177@hanmail.net.
authors.forename: Myung
authors.initials: M
authors.lastname: Im
mesh_terms: D000152:Acne Vulgaris / Q000276:immunology / Q000382:microbiology*; D000328:Adult; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010447:Peptide Hydrolases / Q000378:metabolism; D011425:Propionibacterium acnes / Q000378:metabolism*; D017382:Reactive Oxygen Species; D012627:Sebaceous Glands / Q000166:cytology* / Q000382:microbiology*; D012867:Skin / Q000378:metabolism / Q000382:microbiology; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017382:Reactive Oxygen Species; D010447:Peptide Hydrolases; D020170:Caspase 1