title: Estrogen modulates inflammatory mediator expression and neutrophil chemotaxis in injured arteries.
abstract: BACKGROUND
  We have previously shown that estrogen (17beta-estradiol; E2) inhibits neointima formation and migration of leukocytes, particularly neutrophils, into rat carotid arteries after acute endoluminal injury. This study tested the hypothesis that E2 inhibits expression of adhesion molecules, chemokines, and proinflammatory cytokines in rat carotid arteries in the early hours after balloon injury, thus attenuating the stimulus for leukocyte entry and negatively modulating the injury response.
  
  
  RESULTS
  Ovariectomized (OVX) rats were randomly assigned to treatment with E2 or vehicle (V) and subjected to balloon injury of the right carotid artery. After 2, 6, and 24 hours, rats were euthanized, and both carotid arteries were processed for real-time reverse transcription-polymerase chain reaction (2 and 24 hours), ELISA (6 hours), or neutrophil chemotaxis assay (24 hours). Expression of mRNA for adhesion molecules (P-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1), chemoattractants (cytokine-induced neutrophil chemoattractant [CINC]-2beta and monocyte chemoattractant protein [MCP]-1), and proinflammatory cytokines (interleukin [IL]-1 and IL-6) was markedly increased (2 to 5000 times) in injured arteries of OVX+V rats at 2 hours and was reduced by 24 hours. E2 significantly attenuated expression of the proinflammatory mediators (by 60% to 80%) at 2 hours. ELISA confirmed injury-induced upregulation of neutrophil and monocyte/macrophage chemoattractants (CINC-2alpha, MCP-1) in OVX+V arteries and E2-induced inhibition of CINC-2alpha expression. E2 significantly (by 65%) inhibited neutrophil chemotactic activity of arterial homogenates.
  
  
  CONCLUSIONS
  E2 attenuates the early vascular injury response, at least in part, by negatively modulating proinflammatory mediator expression and the resultant chemotactic activity of injured vessels for neutrophils.
authors.affiliation: Vascular Biology and Hypertension Program, University of Alabama at Birmingham, 1047 Zeigler Research Bldg, 703 19th St S, Birmingham, AL 35294-0007, USA. apmiller@uab.edu
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Miller
authors.forename: Wenguang
authors.initials: W
authors.lastname: Feng
authors.forename: Dongqi
authors.initials: D
authors.lastname: Xing
authors.forename: Nathaniel M
authors.initials: NM
authors.lastname: Weathington
authors.forename: J Edwin
authors.initials: JE
authors.lastname: Blalock
authors.forename: Yiu-Fai
authors.initials: YF
authors.lastname: Chen
authors.forename: Suzanne
authors.initials: S
authors.lastname: Oparil
mesh_terms: D000818:Animals; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002404:Catheterization / Q000009:adverse effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics; D002630:Chemotactic Factors / Q000096:biosynthesis / Q000235:genetics; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D018836:Inflammation Mediators / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D009504:Neutrophils / Q000187:drug effects; D010052:Ovariectomy; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: C491766:Ccl2 protein, rat; D015815:Cell Adhesion Molecules; D018932:Chemokine CCL2; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D007378:Interleukins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol