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Expression of Protease-Activated Receptor-2 in SZ95 Sebocytes and its Role in Sebaceous Lipogenesis, Inflammation, and Innate Immunity.
J Invest Dermatol. 2015 Sep; 135(9):2219-2227.JI

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+Show Affiliations

Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea. Electronic address: ydshderm@yuhs.ac.Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.Research Division Neopharm, Daejeon, Korea.Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea.Departments of Dermatology, Venereology, Allergology, and Immunology, Dessau Medical Center, Dessau, Germany.Department of Dermatology and Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Korea.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25880702

Citation

Lee, Sang E., et al. "Expression of Protease-Activated Receptor-2 in SZ95 Sebocytes and Its Role in Sebaceous Lipogenesis, Inflammation, and Innate Immunity." The Journal of Investigative Dermatology, vol. 135, no. 9, 2015, pp. 2219-2227.
Lee SE, Kim JM, Jeong SK, et al. Expression of Protease-Activated Receptor-2 in SZ95 Sebocytes and its Role in Sebaceous Lipogenesis, Inflammation, and Innate Immunity. J Invest Dermatol. 2015;135(9):2219-2227.
Lee, S. E., Kim, J. M., Jeong, S. K., Choi, E. H., Zouboulis, C. C., & Lee, S. H. (2015). Expression of Protease-Activated Receptor-2 in SZ95 Sebocytes and its Role in Sebaceous Lipogenesis, Inflammation, and Innate Immunity. The Journal of Investigative Dermatology, 135(9), 2219-2227. https://doi.org/10.1038/jid.2015.151
Lee SE, et al. Expression of Protease-Activated Receptor-2 in SZ95 Sebocytes and Its Role in Sebaceous Lipogenesis, Inflammation, and Innate Immunity. J Invest Dermatol. 2015;135(9):2219-2227. PubMed PMID: 25880702.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression of Protease-Activated Receptor-2 in SZ95 Sebocytes and its Role in Sebaceous Lipogenesis, Inflammation, and Innate Immunity. AU - Lee,Sang E, AU - Kim,Ji-Min, AU - Jeong,Se K, AU - Choi,Eung H, AU - Zouboulis,Christos C, AU - Lee,Seung H, Y1 - 2015/04/16/ PY - 2015/01/28/received PY - 2015/03/17/revised PY - 2015/04/07/accepted PY - 2015/4/17/entrez PY - 2015/4/17/pubmed PY - 2015/11/18/medline SP - 2219 EP - 2227 JF - The Journal of investigative dermatology JO - J. Invest. Dermatol. VL - 135 IS - 9 N2 - 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. SN - 1523-1747 UR - https://www.unboundmedicine.com/medline/citation/25880702/Expression_of_Protease_Activated_Receptor_2_in_SZ95_Sebocytes_and_its_Role_in_Sebaceous_Lipogenesis_Inflammation_and_Innate_Immunity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-202X(15)39002-3 DB - PRIME DP - Unbound Medicine ER -