title: Preeclampsia is associated with a deficiency of lipoxin A4, an endogenous anti-inflammatory mediator.
abstract: OBJECTIVE
  To test whether lipoxin A4 (LXA4) deficiency results in preeclampsia.
  
  
  METHODS
  Prospective experimental study.
  
  
  METHODS
  Patient and animal research facilities.
  
  
  METHODS
  Sprague-Dawley rats.
  
  
  METHODS
  We measured LXA4 and its biosynthetic enzymes, blocked the LXA4 signaling pathway, treated experimental rats with preeclampsia with LXA4, and detected inflammatory factors, FPR2/ALX, and 11β-HSD2 to systematically test whether lack of LXA4 results in preeclampsia.
  
  
  METHODS
  We measured serum levels of LXA4 and inflammatory factors using enzyme-linked immunosorbent assay; detected LXA4 biosynthetic enzymes, inflammatory factors, FPR2/ALX, and 11β-HSD2 mRNA expression using reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR; and localized protein expression using immunohistochemistry.
  
  
  RESULTS
  FPR2/ALX and LXA4 and its biosynthetic enzymes were found to be decreased in women with preeclampsia. Replenishing LXA4 improved the symptoms of lipopolysaccharide-induced rats with preeclampsia, while blocking LXA4 signaling resulted in preeclampsia. LXA4 significantly reduced interleukin-6 (IL-6), tumor necrosis factor-α, and IFN-γ but increased IL-10, LXA4 up-regulated 11β-HSD2.
  
  
  CONCLUSIONS
  A deficiency of LXA4 may result in preeclampsia, which might be ascribed to a reduction in inflammation response, oxidative stress, and regulation of 11β-HSD2.
authors.affiliation: Department of Gynecology and Obstetrics, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
authors.forename: Zhangye
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Traumatic Surgery, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Department of Gynecology and Obstetrics, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
authors.affiliation: Department of Gynecology and Obstetrics, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
authors.forename: Huiqiu
authors.initials: H
authors.lastname: Xiang
authors.affiliation: Department of Gynecology and Obstetrics, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China.
authors.forename: Ni
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Duyun
authors.initials: D
authors.lastname: Ye
authors.affiliation: Department of Gynecology and Obstetrics, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China. Electronic address: yphuangp@126.com.
authors.forename: Yinping
authors.initials: Y
authors.lastname: Huang
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001091:Arachidonate Lipoxygenases / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides; D044045:Lipoxins / Q000097:blood / Q000172:deficiency* / Q000494:pharmacology; D011225:Pre-Eclampsia / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044067:Receptors, Lipoxin / Q000097:blood; D015398:Signal Transduction; D013997:Time Factors; D014327:Trophoblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: C530770:5(S),6(R)-7-trihydroxyheptanoic acid, methyl ester; D015415:Biomarkers; D006538:Heptanoic Acids; D018836:Inflammation Mediators; D015850:Interleukin-6; D008070:Lipopolysaccharides; D044045:Lipoxins; D012333:RNA, Messenger; D044067:Receptors, Lipoxin; D014409:Tumor Necrosis Factor-alpha; C482540:lipoxin A(4) receptor, rat; C040527:lipoxin A4; D007371:Interferon-gamma; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468387:HSD11B2 protein, human; D001091:Arachidonate Lipoxygenases
keywords: 11β-HSD1; 11β-HSD2; Preeclampsia; inflammation; lipoxin A4