title: Regulation of stearoyl-coenzyme A desaturase and fatty acid delta-6 desaturase-2 expression by linoleic acid and arachidonic acid in human sebocytes leads to enhancement of proinflammatory activity but does not affect lipogenesis.
abstract: BACKGROUND
  Treatment of SZ95 sebocytes with the essential fatty acid linoleic acid (LA) and the polyunsaturated fatty acid arachidonic acid (AA) leads to sebaceous lipogenesis. Animal data indicate that stearoyl-coenzyme A desaturase (SCD), a key enzyme in fatty acid biosynthesis, is involved in sebaceous lipogenesis and proinflammatory signalling in the sebaceous gland. On the other hand, fatty acid delta-6 desaturase-2 (FADS2) catalyses the conversion of LA to AA.
  
  
  OBJECTIVE
  To identify the effects of LA and AA on the expression of SCD and FADS2 and to detect its biological relevance.
  
  
  METHODS
  SZ95 sebocytes were treated with LA (10(-5) and 10(-4) mol L(-1) ), AA (10(-6) and 10(-5) mol L(-1) ) and the combination of LA (10(-4) mol L(-1) ) and testosterone (2 × 10(-8) mol L(-1) ), with or without addition of the SCD inhibitor FPCA (10(-8) and 10(-6) mol L(-1) ). Cytotoxicity was determined by the lactate dehydrogenase assay. SCD and FACS2 mRNA levels were assessed by semiquantitative reverse transcription-polymerase chain reaction and protein expression by Western blot analysis. SZ95 sebocyte lipid content and cell number were measured by the Nile red and the fluorescein diacetate microassays, respectively. Determination of interleukin (IL)-6 and IL-8 release was evaluated by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  LA treatment induced an increase of SCD and FADS2 at mRNA and protein levels in SZ95 sebocytes after 1·5 h. Treatment with AA led to an increase of SCD but to a decrease of FADS2 mRNA levels. LA/testosterone cotreatment stimulated lipogenesis in SZ95 sebocytes. A distinct proinflammatory pattern was registered: whereas LA strongly upregulated IL-6 secretion only, AA induced a mild level of IL-6 and IL-8 release from SZ95 sebocytes. Treatment with the SCD inhibitor FPCA reduced the LA/testosterone-upregulated SCD and FADS2 mRNA levels and resulted in an anti-inflammatory effect, but did not affect sebaceous lipogenesis.
  
  
  CONCLUSIONS
  LA-induced sebaceous lipogenesis is likely to be an SCD-independent effect. Regulation of SCD and FADS2 expression by LA and AA leads to enhancement of proinflammatory activity but does not affect lipogenesis in human sebocytes.
authors: Department of Dermatology, Dessau Medical Center, Auenweg 38, 06847 Dessau, Germany. christos.zouboulis@klinikum-dessau.de
authors: C C
authors: CC
authors: Zouboulis
authors: S
authors: S
authors: Angres
authors: H
authors: H
authors: Seltmann
mesh_terms: D000214:Acyl Coenzyme A / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D000728:Androgens / Q000494:pharmacology; D016718:Arachidonic Acid / Q000494:pharmacology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D019787:Linoleic Acid / Q000494:pharmacology*; D050602:Linoleoyl-CoA Desaturase / Q000187:drug effects / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects; D050155:Lipogenesis / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D012627:Sebaceous Glands / Q000166:cytology / Q000201:enzymology*; D013739:Testosterone / Q000494:pharmacology
chemical_list: D000214:Acyl Coenzyme A; D000728:Androgens; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D016718:Arachidonic Acid; C017725:stearoyl-coenzyme A; D013739:Testosterone; D019787:Linoleic Acid; D050602:Linoleoyl-CoA Desaturase