title: 15-Lipoxygenase-2 expression in human macrophages induces chemokine secretion and T cell migration.
abstract: BACKGROUND
  We determined previously that hypoxia results in increased 15-lipoxygenase type 2 (15-LOX-2) expression and CXCL8 secretion in macrophages. This study sought to determine whether 15-LOX-2 expression links directly with the secretion of inflammatory molecules in macrophages and also investigated its subsequent effects on T cell migration.
  
  
  METHODS
  Adenovirus-mediated gene delivery caused overexpression of 15-LOX-2 in human macrophages. We used cytometric bead array to measure chemokine secretion, and assessed T cell migration by counting cells in chemotaxis chambers. Expression of chemokine receptors was determined by FACS analysis. Using siRNA, we reduced 15-LOX-2 expression in human macrophages. We used scrambled siRNA as control.
  
  
  RESULTS
  Macrophages that overexpress 15-LOX-2 showed increased secretion of chemokine CXCL10 after 24h incubation. In addition, preconditioned medium from 15-LOX-2-overexpressing cells increased T cell migration and surface expression of CXCR3, the CXCL10 receptor. Knockdown of 15-LOX-2 expression decreased CXCL10 secretion from hypoxic macrophages and also reduced T cell migration.
  
  
  CONCLUSIONS
  In macrophages, overexpression of 15-LOX-2 results in increased secretion of CXCL10 and CCL2. Products released in response to increased 15-LOX-2 activation lead to increased expression of CD69, the T cell activation marker as well as increased T cell migration. Therefore, increased expression of 15-LOX-2 induced by hypoxia may participate in T cell recruitment in diseases such as atherosclerosis.
authors: Sahlgrenska Centre for Cardiovascular and Metabolic Research, Wallenberg Laboratory, The Sahlgrenska Academy, SE-413 45 Göteborg, Sweden.
authors: Kristina Norén
authors: KN
authors: Danielsson
authors: Ellen Knutsen
authors: EK
authors: Rydberg
authors: Madeleine
authors: M
authors: Ingelsten
authors: Levent M
authors: LM
authors: Akyürek
authors: Pernilla
authors: P
authors: Jirholt
authors: Christina
authors: C
authors: Ullström
authors: Gun-Britt
authors: GB
authors: Forsberg
authors: Jan
authors: J
authors: Borén
authors: Olov
authors: O
authors: Wiklund
authors: Lillemor Mattsson
authors: LM
authors: Hultén
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D015703:Antigens, CD / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D001093:Arachidonate 15-Lipoxygenase / Q000235:genetics* / Q000378:metabolism; D050197:Atherosclerosis / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D002450:Cell Communication / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D037181:Lectins, C-Type; D008264:Macrophages / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D034741:RNA, Small Interfering; D019076:Transgenes; D014657:Vasculitis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001093:Arachidonate 15-Lipoxygenase; D054357:Chemokine CXCL10; D016209:Interleukin-8; D037181:Lectins, C-Type; D034741:RNA, Small Interfering; D000099192:CD69 Antigens; C114753:CXCL10 protein, human; C508606:CXCL8 protein, human; C458528:ALOX15B protein, human