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Protease-activated receptor-2 mediates the expression of inflammatory cytokines, antimicrobial peptides, and matrix metalloproteinases in keratinocytes in response to Propionibacterium acnes

 Sang Eun Lee  ;  Ji-Min Kim  ;  Se Kyoo Jeong  ;  Jeong Eun Jeon  ;  Hyun-Ju Yoon  ;  Min-Kyung Jeong  ;  Seung Hun Lee 
 ARCHIVES OF DERMATOLOGICAL RESEARCH, Vol.302(10) : 745-756, 2010 
Journal Title
Issue Date
Acne Vulgaris/immunology* ; Antigens, Bacterial/immunology ; Antimicrobial Cationic Peptides/genetics ; Antimicrobial Cationic Peptides/immunology ; Antimicrobial Cationic Peptides/metabolism ; Calcium Signaling/drug effects ; Calcium Signaling/immunology ; Cell Line, Transformed ; Cytokines/genetics ; Cytokines/immunology ; Cytokines/metabolism ; Gene Expression Regulation/drug effects ; Gene Expression Regulation/immunology ; Gram-Positive Bacterial Infections/immunology* ; Humans ; Inflammation Mediators/immunology ; Inflammation Mediators/metabolism ; Keratinocytes/drug effects ; Keratinocytes/immunology ; Keratinocytes/metabolism* ; Keratinocytes/pathology ; Matrix Metalloproteinases/genetics ; Matrix Metalloproteinases/immunology ; Matrix Metalloproteinases/metabolism ; Propionibacterium acnes/immunology* ; Receptor, PAR-2/antagonists & inhibitors ; Receptor, PAR-2/genetics ; Receptor, PAR-2/immunology ; Receptor, PAR-2/metabolism* ; Serine Proteinase Inhibitors/pharmacology
Antimicrobial peptide ; Cytokine ; Matrix metalloproteinase ; Propionibacterium acnes ; Protease-activated receptor-2
Propionibacterium acnes (P. acnes) has been known to produce various exogenous proteases, however, their role in acne pathogenesis remains largely unknown. Proteases elicit cellular responses, at least in part, via proteinase-activated receptor-2 (PAR-2), which is known to mediate inflammation and immune response. In this study, we investigated whether proteases from P. acnes could activate PAR-2 on keratinocytes and induce pro-inflammatory cytokines, antimicrobial peptides (AMPs), and matrix metalloproteinases (MMPs) via PAR-2 signaling. We examined PAR-2 expression and protease activity in acne lesions using immunofluorescence staining and in situ zymography. The effect of the culture supernatant of P. acnes on Ca(2+) signaling in immortalized keratinocytes (HaCaT) was measured using a fluorescence method. HaCaT cells were treated with P. acnes strain ATCC 6919 culture supernatant, with or without pretreatment with serine protease inhibitor or selective PAR-2 antagonist and the gene expression of pro-inflammatory cytokines, AMPs, and MMPs was detected using real-time reverse transcription-polymerase chain reaction. We found that the protease activity and PAR-2 expression were increased in acne lesions. The P. acnes culture supernatant induced calcium signaling in keratinocytes via PAR-2 and stimulated the mRNA expression of interleukin (IL)-1α, -8, tumor necrosis factor (TNF)-α, human beta defensin (hBD)-2, LL-37, MMP-1, -2, -3, -9, and -13 in keratinocytes, which was significantly inhibited by serine protease inhibitor as well as selective PAR-2 specific antagonist. These results indicate that PAR-2 plays an important role in the pathogenesis of acne by inducing inflammatory mediators in response to proteases secreted from P. acnes.
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1. College of Medicine (의과대학) > Dept. of Dermatology (피부과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Sang Eun(이상은) ORCID logo https://orcid.org/0000-0003-4720-9955
Lee, Seung Hun(이승헌)
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