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A role for lipoxin A 4 as anti‐inflammatory and proresolution mediator in human parturition
Author(s) -
MaldonadoPérez David,
Golightly Ellen,
Denison Fiona C.,
Jabbour Henry N.,
Norman Jane E.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.10-170340
Subject(s) - lipoxin , myometrium , proinflammatory cytokine , inflammation , receptor , endocrinology , medicine , basal (medicine) , uterus , andrology , chemistry , insulin
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 myome‐trial protein release using ELISA, quantified lipoxin receptor (FPR2/ALX) mRNA expression using qRT‐PCR, and localized protein expression using immuno‐histochemstry 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.—Maldonado‐Perez, D., Golightly, E., Denison, F. C., Jabbour, H. N., Norman, J. E. Arole for lipoxin A 4 as anti‐inflammatory and proresolution mediator in human parturition. FASEB J. 25, 569–575 (2011). www.fasebj.org