title: Serglycin secretion is part of the inflammatory response in activated primary human endothelial cells in vitro.
abstract: BACKGROUND
  Endothelial cells have important functions in e.g. regulating blood pressure, coagulation and host defense reactions. Serglycin is highly expressed by endothelial cells, but there is limited data on the roles of this proteoglycan in immune reactions.
  
  
  METHODS
  Cultured primary human endothelial cells were exposed to proinflammatory agents lipopolysaccharide (LPS) and interleukin 1β (IL-1β). The response in serglycin synthesis, secretion and intracellular localization and effect on the proteoglycan binding chemokines CXCL-1 and CXCL-8 were determined by qRT-PCR, Western blotting, immunocytochemistry, ELISA and serglycin knockdown experiments.
  
  
  RESULTS
  Both LPS and IL-1β increased the synthesis and secretion of serglycin, while only IL-1β increased serglycin mRNA expression. Stimulation increased the number of serglycin containing vesicles, with a greater portion of large vesicles after LPS treatment. Also, increased intracellular and secreted levels of CXCL-1 and CXCL-8 were observed. The increase in CXCL-8 secretion was unchanged in serglycin knockdown cells. However, the increase in CXCL-1 secretion from IL-1β stimulation was reduced 27% in serglycin knockdown cells; while the LPS-induced secretion was not affected. In serglycin expressing cells CXCL-1 positive vesicles were evenly distributed throughout the cytoplasm, while confided to the Golgi region in serglycin knockdown cells. This was the case only for IL-1β stimulated cells. LPS-induced CXCL-1 distribution was unaffected by serglycin expression.
  
  
  CONCLUSIONS
  These results suggest that different signaling pathways are involved in regulating secretion of serglycin and partner molecules in activated endothelial cells.
  
  
  CONCLUSIONS
  This knowledge increases our understanding of the roles of serglycin in immune reactions. This article is part of a Special Issue entitled: Matrix-mediated cell behaviour and properties.
authors: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Box 1046, Blindern, 0316 Oslo, Norway.
authors: Trine M
authors: TM
authors: Reine
authors: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Box 1046, Blindern, 0316 Oslo, Norway.
authors: Tram Thu
authors: TT
authors: Vuong
authors: Department of Transplant Medicine, Section of Nephrology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Health Science, University of Tromsø, Tromsø, Norway.
authors: Trond G
authors: TG
authors: Jenssen
authors: Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Box 1046, Blindern, 0316 Oslo, Norway. Electronic address: s.o.kolset@medisin.uio.no.
authors: Svein O
authors: SO
authors: Kolset
mesh_terms: D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000378:metabolism; D055785:Gene Knockdown Techniques; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology*; D053583:Interleukin-1beta / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D011509:Proteoglycans / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: C475829:CXCL1 protein, human; C508606:CXCL8 protein, human; D054360:Chemokine CXCL1; D053583:Interleukin-1beta; D016209:Interleukin-8; D008070:Lipopolysaccharides; D011509:Proteoglycans; D033921:Vesicular Transport Proteins; C075430:serglycin
keywords: Chemokine; Inflammation; Interleukin-1 beta; Lipopolysaccharide; Primary human endothelial cell; Serglycin