Alterations in IL-4, IL-10 and IFN-γ levels synergistically decrease lipid content and protein expression of FAS and mature SREBP-1 in human sebocytes

Arch Dermatol Res. 2019 Sep;311(7):563-571. doi: 10.1007/s00403-019-01932-x. Epub 2019 May 24.

Abstract

When anti-acne alternatives from dietary and plant sources are ingested, systemic alterations of interleukin (IL)-4, IL-10, IL-12 and interferon (IFN)-γ, individually or simultaneously, are induced at a 0.1-10.0-fold (×) range of normal physiological concentrations (1×). However, little is known about the effects of these cytokines on excess sebum, a pathophysiological factor of acne development. In this study, human sebocytes were treated with 0.1-10.0× of IL-4, IL-10, IL-12 and IFN-γ for 3 or 5 days to elucidate the effects on lipid content. Treatment with individual cytokines decreased the lipid content at specific concentrations rather than in a concentration-dependent manner. Specifically, 5.0× of IL-4, 5.0× of IFN-γ (5.0IFN), and 0.5×, 5.0× and 10.0× of IL-10 for 3 days, and 0.5× of IL-4 (0.5IL4) for 5 days decreased lipid content to 87.6-93.0% of the control. Treatment with other concentrations of IL-4, IL-10 and IFN-γ, and 0.1-10.0× of IL-12 did not alter lipid content. Combined treatment with 0.5IL4, 5.0IFN and 0.5× of IL-10 for 3 or 5 days decreased the lipid content more than each individual treatment. However, this effect was more evident after 3 days, in parallel with decreased levels of triglycerides, cholesterol esters and free fatty acids, the major lipid compositions of sebocytes, and decreased protein expression of fatty acid synthase (FAS) and mature sterol response element-binding protein-1 (SREBP-1), the lipogenesis-related factors, without altered cell proliferation. We demonstrated that suppressed IL-4 and IL-10 with enhanced IFN-γ synergistically decreased lipid content and protein expression of FAS and mature SREBP-1 in human sebocytes.

Keywords: Cytokines; FAS; Lipid content; Mature SREBP-1; Sebocytes; Synergism.

MeSH terms

  • Acne Vulgaris / diet therapy
  • Acne Vulgaris / immunology
  • Acne Vulgaris / pathology
  • Cell Line
  • Cell Proliferation
  • Fatty Acid Synthases / metabolism*
  • Humans
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-10 / immunology
  • Interleukin-10 / metabolism
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism
  • Lipids / analysis
  • Lipogenesis / immunology
  • Primary Cell Culture
  • Sebaceous Glands / cytology
  • Sebaceous Glands / immunology
  • Sebaceous Glands / metabolism*
  • Sebum / chemistry
  • Sebum / immunology
  • Sebum / metabolism*
  • Sterol Regulatory Element Binding Protein 1 / metabolism*

Substances

  • IFNG protein, human
  • IL10 protein, human
  • IL4 protein, human
  • Lipids
  • SREBF1 protein, human
  • Sterol Regulatory Element Binding Protein 1
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma
  • Fatty Acid Synthases