Tumor necrosis factor-alpha (TNF-α) is an important pathophysiologic factor involved in the development of acne. However, its role is unclear.
To explore the lipogenic effect by TNF-α and possible molecular mechanisms in sebocyte.
Using SZ95 human sebocytes, lipid formation by TNF-α was assessed by Oil Red O, Nile Red staining and thin layer chromatography (TLC). Expression of lipogenic genes and activation of mitogen-activated protein kinase as well as Akt were examined by real-time polymerase chain reaction and/or Western blot analysis. Activation of peroxisome proliferator-activated receptor (PPAR) was evaluated by luciferase assay using PPAR response element containing reporter plasmids. Involvement of c-Jun N-terminal kinase (JNK) and Akt in TNF-α-induced lipogenesis was investigated by molecule specific small interfering RNA and inhibitors.
TNF-α treatment significantly increased formation of lipid droplets in accordance with up-regulated expression of FAS and activation of SREBP-1, but not PPARs. Suppression of phosphorylated JNK by the JNK inhibitor SP600125 greatly diminished TNF-α-induced expression of FAS and SREBP-1. TNF-α could not induce both expression of lipogenic proteins and lipid synthesis when Akt expression was attenuated with siRNA.
TNF-α induces lipogenesis in SZ95 human sebocytes through the JNK and phosphoinositide-3-kinase/Akt pathways. These results will be valuable in developing therapeutic strategies for control of seborrhea and acne.
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- Thematic review series: skin lipids. Sebaceous gland lipids: friend or foe?.J Lipid Res. 2008; 49: 271-281
- Sebocytes, multifaceted epithelial cells: lipid production and holocrine secretion.Int J Biochem Cell Biol. 2010; 42: 181-185
- Sexual hormones in human skin.Horm Metab Res. 2007; 39: 85-95
- Insulin-like growth factor-1 induces lipid production in human SEB-1 sebocytes via sterol response element-binding protein-1.J Invest Dermatol. 2006; 126: 1226-1232
- Interplay of IGF-I and 17beta-estradiol at age-specific levels in human sebocytes and fibroblasts in vitro.Exp Gerontol. 2008; 43: 939-946
- Enzymes involved in the biosynthesis of leukotriene B4 and prostaglandin E2 are active in sebaceous glands.J Mol Med. 2006; 84: 75-87
- Zileuton, an oral 5-lipoxygenase inhibitor, directly reduces sebum production.Dermatology. 2005; 210: 36-38
- Expression of peroxisome proliferator-activated receptor and CCAAT/enhancer binding protein transcription factors in cultured human sebocytes.J Invest Dermatol. 2003; 121: 441-447
- Expression of lipogenic factors galectin-12, resistin, SREBP-1, and SCD in human sebaceous glands and cultured sebocytes.J Invest Dermatol. 2007; 127: 1309-1317
- Peroxisome proliferators-activated receptor (PPAR) modulators and metabolic disorders.PPAR Res. 2008; : 679137
- Peroxisome proliferator-activated receptors increase human sebum production.J Invest Dermatol. 2006; 126: 2002-2009
- LXRalpha enhances lipid synthesis in SZ95 sebocytes.J Invest Dermatol. 2008; 128: 1266-1272
- Propionibacterium acnes and lipopolysaccharide induce the expression of antimicrobial peptides and proinflammatory cytokines/chemokines in human sebocytes.Microbes Infect. 2006; 8: 2195-2205
- Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses.J Immunol. 2002; 169: 1535-1541
- Corynebacterium parvum (Propionibacterium acnes): an inducer of tumor necrosis factor-alpha in human peripheral blood mononuclear cells and monocytes in vitro.Eur J Immunol. 1990; 20: 1761-1765
- Proinflammatory cytokine production by human keratinocytes stimulated with Propionibacterium acnes and P. acnes GroEL.Br J Dermatol. 2004; 150: 421-428
- Inflammatory events are involved in acne lesion initiation.J Invest Dermatol. 2003; 121: 20-27
- Establishment and characterization of an immortalized human sebaceous gland cell line (SZ95).J Invest Dermatol. 1999; 113: 1011-1020
- IGF-1 induces SREBP-1 expression and lipogenesis in SEB-1 sebocytes via activation of the phosphoinositide 3-kinase/Akt pathway.J Invest Dermatol. 2008; 128: 1286-1293
- The sebocyte culture: a model to study the pathophysiology of the sebaceous gland in sebostasis, seborrhoea and acne.Arch Dermatol Res. 2008; 300: 397-413
- Sterol regulation of fatty acid synthase promoter. Coordinate feedback regulation of two major lipid pathways.J Biol Chem. 1995; 270: 25578-25583
- MAP kinase activation in macrophages.J Leukoc Biol. 2001; 69: 3-10
- Activation of the AP-1 transcription factor by inflammatory cytokines of the TNF family.Gene Expr. 1999; 7: 217-231
- KGF induces lipogenic genes through a PI3K and JNK/SREBP-1 pathway in H292 cells.J Lipid Res. 2005; 46: 2624-2635
- Sterol regulatory element binding proteins (SREBP)-1a and SREBP-2 are linked to the MAP-kinase cascade.J Lipid Res. 2000; 41: 99-108
- Severe acne successfully treated with etanercept.Acta Derm Venereol. 2006; 86: 256-257
- Inflammation and extracellular matrix degradation mediated by activated transcription factors nuclear factor-kappaB and activator protein-1 in inflammatory acne lesions in vivo.Am J Pathol. 2005; 166: 1691-1699
- Different pro-inflammatory and immunogenic potentials of Propionibacterium acnes and Staphylococcus epidermidis: implications for chronic inflammatory acne.Arch Immunol Ther Exp (Warsz). 2005; 53: 79-85
- Induction of proinflammatory cytokines by a soluble factor of Propionibacterium acnes: implications for chronic inflammatory acne.Infect Immun. 1995; 63: 3158-3165
- Pu-erh tea supplementation suppresses fatty acid synthase expression in the rat liver through downregulating Akt and JNK signalings as demonstrated in human hepatoma HepG2 cells.Oncol Res. 2005; 16: 119-128
- Specific inhibitors of p38 mitogen-activated protein kinase block 3T3-L1 adipogenesis.J Biol Chem. 1998; 273: 32111-32120
- PI3K/Akt pathway mediates high glucose-induced lipogenesis and extracellular matrix accumulation in HKC cells through regulation of SREBP-1 and TGF-beta1.Histochem Cell Biol. 2011; 135: 173-181
- Androgen stimulates glycolysis for de novo lipid synthesis by increasing the activities of hexokinase 2 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 in prostate cancer cells.Biochem J. 2010; 433: 225-233
- Expression of a constitutively active Akt Ser/Thr kinase in 3T3-L1 adipocytes stimulates glucose uptake and glucose transporter 4 translocation.J Biol Chem. 1996; 271: 31372-31378
- PKB/Akt induces transcription of enzymes involved in cholesterol and fatty acid biosynthesis via activation of SREBP.Oncogene. 2005; 24: 6465-6481
- Involvement of Akt in ER-to-Golgi transport of SCAP/SREBP: a link between a key cell proliferative pathway and membrane synthesis.Mol Biol Cell. 2006; 17: 2735-2745
- Modelling the remission of individual acne lesions in vitro.Br J Dermatol. 2002; 147: 869-878
- The effects of inflammatory cytokines on the isolated human sebaceous infundibulum.J Invest Dermatol. 1998; 110: 410-415
- Mechanisms by which tumor necrosis factor stimulates hepatic fatty acid synthesis in vivo.J Lipid Res. 1988; 29: 1327-1335
- TNF-alpha induces hepatic steatosis in mice by enhancing gene expression of sterol regulatory element binding protein-1c (SREBP-1c).Exp Biol Med (Maywood). 2007; 232: 614-621
- Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-alpha.Cytokine Growth Factor Rev. 2003; 14: 447-455
- Human obesity and type 2 diabetes are associated with alterations in SREBP1 isoform expression that are reproduced ex vivo by tumor necrosis factor-alpha.Diabetes. 2002; 51: 1035-1041
- Infliximab-induced acne: report of a third case.Br J Dermatol. 2008; 158: 172
- Infliximab-induced acne: report of two cases.Br J Dermatol. 2007; 156: 402-403
- Infliximab-induced acne: a new case and review of published reports.J Dermatolog Treat. 2009; 20: 59-60
Published online: February 03, 2012
Accepted: November 12, 2011
Received in revised form: November 11, 2011
Received: June 29, 2011
© 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Inc. All rights reserved.