title: Expression of Protease-Activated Receptor-2 in SZ95 Sebocytes and its Role in Sebaceous Lipogenesis, Inflammation, and Innate Immunity.
abstract: Protease-activated receptor-2 (PAR-2) functions as innate biosensor for proteases and regulates numerous functions of the skin. However, the expression and physiological role of PAR-2 in sebocytes remain to be elucidated. Here, we identified PAR-2 expression in SZ95 sebocytes at both mRNA and protein levels. Intracellular Ca(2+) mobilization by PAR-2 agonist peptide (PAR-2 AP) or Propionibacterium acnes (P. acnes) culture supernatant was detected, indicating that P. acnes is a potent activator of PAR-2 on sebocytes. The small interfering RNA (siRNA)-mediated PAR-2 knockdown in sebocytes resulted in defective differentiation and lipogenesis. PAR-2 AP treatment enhanced lipogenesis and sterol response element-binding protein-1 (SREBP-1) expression, suggesting a role of PAR-2 in the differentiation and lipogenesis of sebocytes. Moreover, PAR-2 AP induced cytokines and human β-defensin-2 (hBD-2) transcription in sebocytes. PAR-2 expression was increased in sebaceous glands of acne lesions. PAR-2 silencing by siRNA abrogated the increase in sebaceous lipogenesis and SREBP-1 expression by P. acnes supernatant. PAR-2 knockdown also inhibited the P. acnes supernatant-induced expression of cytokines and hBD-2. In conclusion, PAR-2 is expressed in SZ95 sebocytes and mediates differentiation, lipogenesis, inflammation, and innate immunity in response to P. acnes. Therefore, PAR-2 might be a therapeutic target for sebaceous gland disorders such as acne.
authors.affiliation: Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea. Electronic address: ydshderm@yuhs.ac.
authors.forename: Sang E
authors.initials: SE
authors.lastname: Lee
authors.affiliation: Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Kim
authors.affiliation: Research Division Neopharm, Daejeon, Korea.
authors.forename: Se K
authors.initials: SK
authors.lastname: Jeong
authors.affiliation: Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Eung H
authors.initials: EH
authors.lastname: Choi
authors.affiliation: Departments 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 and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Seung H
authors.initials: SH
authors.lastname: Lee
mesh_terms: D000152:Acne Vulgaris / Q000276:immunology* / Q000382:microbiology; D001707:Biopsy, Needle; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics* / Q000502:physiology; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics* / Q000276:immunology; D050155:Lipogenesis / Q000235:genetics* / Q000276:immunology; D011425:Propionibacterium acnes / Q000276:immunology; D034741:RNA, Small Interfering / Q000032:analysis; D044464:Receptor, PAR-2 / Q000235:genetics*; D012627:Sebaceous Glands / Q000166:cytology* / Q000378:metabolism*; D012680:Sensitivity and Specificity; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D044464:Receptor, PAR-2; D051780:Sterol Regulatory Element Binding Protein 1