Ann Dermatol.  2017 Feb;29(1):20-25. 10.5021/ad.2017.29.1.20.

Insulin-Like Growth Factor-1 Increases the Expression of Inflammatory Biomarkers and Sebum Production in Cultured Sebocytes

• Kim H
• Moon SY
• Sohn MY
• Lee WJ

• KMID: 2368023
• DOI: http://doi.org/10.5021/ad.2017.29.1.20

Abstract

BACKGROUND
Acne vulgaris has been linked to the Western diet. Hyperglycemic diet increases insulin and insulin-like growth factor (IGF)-1. Deeper insights into IGF-1-mediated signal pathway are critical importance to understand the impact of Western diet.
OBJECTIVE
We investigated the effect of IGF-1 on the expression of inflammatory biomarkers and sebum production in cultured sebocytes.
METHODS
Polymerase chain reaction and enzyme-linked immunosorbent assay were performed to measure changes in the expression of inflammatory biomarkers including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), IGF1R, IGFBP2, sterol response element-binding protein (SREBP), and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3KCA) after the treatment of cultured sebocytes with 10⁻⁷ M or 10⁻⁵ M IGF-1. Sebum production was evaluated after the treatment of cultured sebocytes with 10⁻⁷ M or 10⁻⁵ M IGF-1 using lipid analysis.
RESULTS
The expression levels of IL-1β, IL-6, IL-8, and TNF-α in cultured sebocytes after treatment with 10⁻⁷ M or 10⁻⁵ M IGF-1 were increased. Increased gene expression levels of NF-κB in cultured sebocytes were also shown after 10⁻⁷ M or 10⁻⁵ M IGF-1 treatments. Gene expression of these inflammatory biomarkers was decreased after 10⁻⁷ M or 10⁻⁵ M IGF-1 treatment in the presence of 100 nM NF-κB inhibitor. Treatment with 10⁻⁷ M or 10⁻⁵ M IGF-1 increased the gene expression levels of IGF1R, IGFBP2, SREBP and PI3KCA in cultured sebocytes. Sebum production from cultured sebocytes treated with 10⁻⁷ M or 10⁻⁵ M IGF-1 was also increased.
CONCLUSION
It is suggestive that IGF-1 might be involved in the pathogenesis of acne by increasing both expression of inflammatory biomarkers and also sebum production in sebocytes.

Keyword

Biomarkers; Insulin-like growth factor-1; Sebum

MeSH Terms

Acne Vulgaris
B-Lymphocytes
Biomarkers*
Catalytic Domain
Diet
Diet, Western
Enzyme-Linked Immunosorbent Assay
Gene Expression
Insulin
Insulin-Like Growth Factor I
Interleukin-6
Interleukin-8
Interleukins
Polymerase Chain Reaction
Sebum*
Signal Transduction
Tumor Necrosis Factor-alpha
Biomarkers
Insulin
Insulin-Like Growth Factor I
Interleukin-6
Interleukin-8
Interleukins
Tumor Necrosis Factor-alpha

Figure

• 

  Fig. 1 The increased expression of inflammatory cytokines in cultured sebocytes after treatment with insulin-like growth factor (IGF)-1. (A) The treatment of cultured sebocytes with 10−7 M or 10−5 M IGF-1 showed increased gene expression of interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF)-α. *p<0.05. (B) The treatment of cultured sebocytes with 10−7 M or 10−5 M IGF-1 increased protein expression of IL-1β, IL-6, IL-8 and TNF-α.

• 

  Fig. 2 The decreased expression of inflammatory cytokines after treatment of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibitor-pretreated sebocytes with insulin-like growth factor (IGF)-1. (A) The treatment of cultured sebocytes with 10−7 M IGF-1 showed an increase in the gene expression of NF-κB. The treatment of 100 nM NF-κB inhibitor-pretreated sebocytes with 10−7 M IGF-1 showed a significant decrease in the gene expression of NF-κB, interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α. *p<0.05. (B) The treatment of cultured sebocytes with 10−5 M IGF-1 showed an increase in the gene expression of NF-κB. The treatment of 100 nM NF-κB inhibitor-pretreated sebocytes with 10−5 M IGF-1 showed a significant decrease in the gene expression of NF-κB, IL-1β, IL-6, IL-8, and TNF-α. *p<0.05.

• 

  Fig. 3 The increased expression of insulin-like growth factor (IGF)1R and IGFBP2 in cultured sebocytes after treatment with IGF-1. In addition, the increased gene expression of sterol response element-binding protein (SREBP) and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3KCA) after treatment of cultured sebocytes with IGF-1.

• 

  Fig. 4 The increased lipid production after treatment of cultured sebocytes with insulin-like growth factor (IGF)-1. Lipid production was increased following the treatment of the cultured sebocytes with 10−7 M or 10−5 M IGF-1. *p<0.05.

Reference

1. Winston MH, Shalita AR. Acne vulgaris. Pathogenesis and treatment. Pediatr Clin North Am. 1991; 38:889–903.

2. Zouboulis CC. Acne and sebaceous gland function. Clin Dermatol. 2004; 22:360–366.

3. Zouboulis CC, Adjaye J, Akamatsu H, Moe-Behrens G, Niemann C. Human skin stem cells and the ageing process. Exp Gerontol. 2008; 43:986–997.

4. Kurokawa I, Danby FW, Ju Q, Wang X, Xiang LF, Xia L, et al. New developments in our understanding of acne pathogenesis and treatment. Exp Dermatol. 2009; 18:821–832.

5. Melnik BC. Diet in acne: further evidence for the role of nutrient signalling in acne pathogenesis. Acta Derm Venereol. 2012; 92:228–231.

6. Kwon HH, Yoon JY, Hong JS, Jung JY, Park MS, Suh DH. Clinical and histological effect of a low glycaemic load diet in treatment of acne vulgaris in Korean patients: a randomized, controlled trial. Acta Derm Venereol. 2012; 92:241–246.

7. Smith TM, Gilliland K, Clawson GA, Thiboutot D. 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.

8. Renier G, Clément I, Desfaits AC, Lambert A. Direct stimulatory effect of insulin-like growth factor-I on monocyte and macrophage tumor necrosis factor-alpha production. Endocrinology. 1996; 137:4611–4618.

9. Kooijman R, Coppens A, Hooghe-Peters E. IGF-I stimulates IL-8 production in the promyelocytic cell line HL-60 through activation of extracellular signal-regulated protein kinase. Cell Signal. 2003; 15:1091–1098.

10. Tu W, Cheung PT, Lau YL. IGF-I increases interferon-gamma and IL-6 mRNA expression and protein production in neonatal mononuclear cells. Pediatr Res. 1999; 46:748–754.

11. Im M, Kim SY, Sohn KC, Choi DK, Lee Y, Seo YJ, et al. Epigallocatechin-3-gallate suppresses IGF-I-induced lipogenesis and cytokine expression in SZ95 sebocytes. J Invest Dermatol. 2012; 132:2700–2708.

12. Cappel M, Mauger D, Thiboutot D. Correlation between serum levels of insulin-like growth factor 1, dehydroepiandrosterone sulfate, and dihydrotestosterone and acne lesion counts in adult women. Arch Dermatol. 2005; 141:333–338.

13. Zouboulis CC. Is acne vulgaris a genuine inflammatory disease? Dermatology. 2001; 203:277–279.

14. Zouboulis CC, Eady A, Philpott M, Goldsmith LA, Orfanos C, Cunliffe WC, et al. What is the pathogenesis of acne? Exp Dermatol. 2005; 14:143–152.

15. Webster GF. Inflammation in acne vulgaris. J Am Acad Dermatol. 1995; 33:247–253.

16. Kang S, Cho S, Chung JH, Hammerberg C, Fisher GJ, Voorhees JJ. 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.

17. Rasmussen JE. Diet and acne. Int J Dermatol. 1977; 16:488–492.

18. Pappas A. The relationship of diet and acne: a review. Dermatoendocrinol. 2009; 1:262–267.

19. Liakou AI, Theodorakis MJ, Melnik BC, Pappas A, Zouboulis CC. Nutritional clinical studies in dermatology. J Drugs Dermatol. 2013; 12:1104–1109.

20. Smith R, Mann N, Mäkeläinen H, Roper J, Braue A, Varigos G. A pilot study to determine the short-term effects of a low glycemic load diet on hormonal markers of acne: a nonrandomized, parallel, controlled feeding trial. Mol Nutr Food Res. 2008; 52:718–726.

21. Clarke SB, Nelson AM, George RE, Thiboutot DM. Pharmacologic modulation of sebaceous gland activity: mechanisms and clinical applications. Dermatol Clin. 2007; 25:137–146.

22. Alestas T, Ganceviciene R, Fimmel S, Müller-Decker K, Zouboulis CC. Enzymes involved in the biosynthesis of leukotriene B4 and prostaglandin E2 are active in sebaceous glands. J Mol Med (Berl). 2006; 84:75–87.

23. Lee WJ, Jung HD, Lee HJ, Kim BS, Lee SJ, Kim DW. Influence of substance-P on cultured sebocytes. Arch Dermatol Res. 2008; 300:311–316.

24. Lee WJ, Jung HD, Chi SG, Kim BS, Lee SJ, Kim DW, et al. Effect of dihydrotestosterone on the upregulation of inflammatory cytokines in cultured sebocytes. Arch Dermatol Res. 2010; 302:429–433.

25. Lee WJ, Chae SY, Ryu HS, Jang YH, Lee SJ, Kim DW. Inflammatory cytokine expression and sebum production after exposure of cultured human sebocytes to ultraviolet a radiation and light at wavelengths of 650 nm and 830 nm. Ann Dermatol. 2015; 27:163–170.

26. Mirdamadi Y, Thielitz A, Wiede A, Goihl A, Papakonstantinou E, Hartig R, et al. Insulin and insulin-like growth factor-1 can modulate the phosphoinositide-3-kinase/Akt/FoxO1 pathway in SZ95 sebocytes in vitro. Mol Cell Endocrinol. 2015; 415:32–44.