A role for lipoxin A4 as anti-inflammatory and proresolution mediator in human parturition.
The purpose of this study was to investigate the role of lipoxin A(4), an anti-inflammatory and proresolution modulator, during human parturition. We measured serum levels of lipoxin A(4) and myometrial protein release using ELISA, quantified lipoxin receptor (FPR2/ALX) mRNA expression using qRT-PCR, and localized protein expression using immunohistochemstry in myometrial biopsies from pregnant women. In addition, we compared the effects of lipoxin A(4) (100 nM) with vehicle on basal and LPS-stimulated expression of proinflammatory cytokines from samples of myometrium from pregnant women. Mean ± SE circulating level of lipoxin A(4) was 5.89 ± 0.63 nM at 24-wk gestation, with a further modest increase during pregnancy (P<0.05), but no differences in gestation matched women before and after labor (P>0.05). Levels of lipoxin A(4) in nonpregnant women were 0.48 ± 0.04 nM, significantly lower than in pregnant women (P<0.001). FPR2/ALX localized to myocytes and neutrophils, with a 9-fold increase in mRNA expression in labor (P<0.001). Lipoxin A(4) significantly reduced LPS-induced but not basal expression of the proinflammatory cytokines IL-6 and IL-8 in cultured myometrium (P<0.05), compared to vehicle-treated controls. We demonstrate for the first time a potential role for lipoxin A(4) and its receptor in the resolution of the inflammatory events of both physiological and pathological labor.
Division of Reproductive and Developmental Sciences, University of Edinburgh, Centre for Reproductive Biology, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
David
D
Maldonado-Pérez
Ellen
E
Golightly
Fiona C
FC
Denison
Henry N
HN
Jabbour
Jane E
JE
Norman
D000328:Adult; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007743:Labor, Obstetric / Q000502:physiology*; D008070:Lipopolysaccharides; D044045:Lipoxins / Q000097:blood* / Q000378:metabolism*; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism; D036801:Parturition / Q000502:physiology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044042:Receptors, Formyl Peptide / Q000235:genetics / Q000378:metabolism; D044067:Receptors, Lipoxin / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
C105101:FPR2 protein, human; D008070:Lipopolysaccharides; D044045:Lipoxins; D012333:RNA, Messenger; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; C040527:lipoxin A4