title: Interleukin-5 is a potential mediator of angiotensin II-induced aneurysm formation in apolipoprotein E knockout mice.
abstract: BACKGROUND
  The aim of this study was to evaluate alterations in Th1 and Th2 cytokines during experimental abdominal aortic aneurysm (AAA) formation.
  
  
  METHODS
  AAAs were induced in apolipoprotein E null mice by infusing angiotensin II (Ang II, 1000 ng/kg/min). Aortic homogenates were assessed at 0, 7, 14, and 28 d (n = 11/time point) for select Th1 and Th2 cytokines by ELISA. Additional mice had co-administration of anti-IgG (n = 20) or anti-IL-5 (n = 20) and were assessed at 28 d for AAA. Aortic homogenates were assessed for MMP-2 and MMP-9 expression. Mouse aortic SMC (MASMC) and peritoneal-derived macrophages were treated with IL-5 (0-40 ng/mL), and cell extracts and media (0-48 h) were assessed for MMP-2 and MMP-9 expression.
  
  
  RESULTS
  Ang II infusion was associated with a 3.4-fold (P < 0.01) and 3.6-fold (P < 0.01) increase in IL-5 and IL-10 (respectively), and a 0.6-fold reduction in IL-6, by 7 d. Anti-IL-5, but not anti-IgG, ameliorated Ang II-induced AAA formation. Up-regulation of MMP-2 and MMP-9 was observed in aneurysmal aortas, but not in the aortas obtained from mice treated with anti-IL-5. IL-5 stimulation of MASMC increased MMP-2 and MMP-9 mRNA (2.1-fold and 2.7-fold, respectively, P < 0.01) and protein (1.6-fold and 1.9-fold, respectively, P < 0.01) by 24 h. IL-5 stimulation of macrophages did not alter MMP expression.
  
  
  CONCLUSIONS
  Ang II induces increased Th2 cytokines IL-5 and IL-10 early in the course of experimental AAA formation, and inhibition of IL-5 prevents AAA formation suggesting an important role. While IL-5 is capable of up-regulating MMP-2 and MMP-9 expression in MASMC, investigations into alternate roles in AAA formation is warranted.
authors.affiliation: Department of Vascular Surgery, Cleveland Clinic Lerner College of Medicine-CWRU, Cleveland, Ohio 44195, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Brittney
authors.initials: B
authors.lastname: Ehrman
authors.forename: Linda M
authors.initials: LM
authors.lastname: Graham
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Eagleton
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000166:cytology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism*; D001057:Apolipoproteins E / Q000235:genetics*; D002478:Cells, Cultured; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D015848:Interleukin-5 / Q000276:immunology* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014657:Vasculitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D001057:Apolipoproteins E; C556062:IL10 protein, mouse; D015848:Interleukin-5; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D016753:Interleukin-10; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse