: Acne is the most common skin disease affecting young people. In addition to psychological distress and feelings of low self-esteem, acne can lead to permanent facial scarring. The production of sebum (oil) by sebaceous glands is a key factor in the development of acne. Apart from isotretinoin and hormonal therapy, there are no drugs that effectively reduce sebum production. Unfortunately, these drugs have significant side effects, including birth defects. No recent advances have been made in our ability to therapeutically reduce sebum production in part due to our lack of knowledge regarding the mechanisms regulating human sebum production. The overall goal of this research is to elucidate the mechanisms that regulate human sebum production in order to identify novel therapeutic target sites whose pharmacological ligands will offer safe and effective alternatives to isotretinoin for the treatment of acne. Peroxisome proliferator-activated receptors (PPARs) and sterol response element binding proteins (SREBPs) are key transcriptional regulators of lipid metabolism in a variety of tissues. The central hypothesis to be tested is that PPARs regulate lipid metabolism in human sebaceous glands. The effects of linoleic acid and other PPAR agonists on lipid metabolism will be determined using assays of lipid transport, synthesis, and catabolism in addition to an analysis of gene expression. 13-cis retinoic acid is the most potent sebosuppressive agent. PPARs and retinoids share common DNA binding sites, and in this regard can mediate transcription of common genes. Our secondary hypothesis is that 13-cis retinoic acid reduces sebum production by altering the expression of PPAR-regulated genes. The effects of 13-cis retinoic acid on gene expression will be examined in human sebocytes and in skin from patients treated with isotretinoin. Data generated from the proposed experiments will advance our understanding of the mechanisms regulating sebum production and can lead to identification of potential additional therapeutic target sites in the treatment of acne.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
Project #
Application #
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Moshell, Alan N
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Pennsylvania State University
Schools of Medicine
United States
Zip Code
Dispenza, Melanie C; Wolpert, Ellen B; Gilliland, Kathryn L et al. (2012) Systemic isotretinoin therapy normalizes exaggerated TLR-2-mediated innate immune responses in acne patients. J Invest Dermatol 132:2198-205
Nelson, A M; Cong, Z; Gilliland, K L et al. (2011) TRAIL contributes to the apoptotic effect of 13-cis retinoic acid in human sebaceous gland cells. Br J Dermatol 165:526-33
Lumsden, K R; Nelson, A M; Dispenza, M C et al. (2011) Isotretinoin increases skin-surface levels of neutrophil gelatinase-associated lipocalin in patients treated for severe acne. Br J Dermatol 165:302-10
Nelson, Amanda M; Zhao, Wei; Gilliland, Kathryn L et al. (2009) Isotretinoin temporally regulates distinct sets of genes in patient skin. J Invest Dermatol 129:1038-42
Smith, Terry M; Gilliland, Kathryn; Clawson, Gary A et al. (2008) IGF-1 induces SREBP-1 expression and lipogenesis in SEB-1 sebocytes via activation of the phosphoinositide 3-kinase/Akt pathway. J Invest Dermatol 128:1286-93
Nelson, Amanda M; Zhao, Wei; Gilliland, Kathryn L et al. (2008) Neutrophil gelatinase-associated lipocalin mediates 13-cis retinoic acid-induced apoptosis of human sebaceous gland cells. J Clin Invest 118:1468-78
Smith, Terry M; Cong, Zhaoyuan; Gilliland, Kathryn L et al. (2006) Insulin-like growth factor-1 induces lipid production in human SEB-1 sebocytes via sterol response element-binding protein-1. J Invest Dermatol 126:1226-32
Trivedi, Nishit R; Gilliland, Kathryn L; Zhao, Wei et al. (2006) Gene array expression profiling in acne lesions reveals marked upregulation of genes involved in inflammation and matrix remodeling. J Invest Dermatol 126:1071-9
Trivedi, Nishit R; Cong, Zhaoyuan; Nelson, Amanda M et al. (2006) Peroxisome proliferator-activated receptors increase human sebum production. J Invest Dermatol 126:2002-9
Nelson, Amanda M; Gilliland, Kathryn L; Cong, Zhaoyuan et al. (2006) 13-cis Retinoic acid induces apoptosis and cell cycle arrest in human SEB-1 sebocytes. J Invest Dermatol 126:2178-89