Complement C5a regulates prolabor mediators in human placenta

Lappas, Martha, Woodruff, Trent M., Taylor, Stephen M. and Permezel, Michael (2012) Complement C5a regulates prolabor mediators in human placenta. Biology of Reproduction, 86 6: 190.1-190.9. doi:10.1095/biolreprod.111.098475

Author Lappas, Martha
Woodruff, Trent M.
Taylor, Stephen M.
Permezel, Michael
Title Complement C5a regulates prolabor mediators in human placenta
Journal name Biology of Reproduction   Check publisher's open access policy
ISSN 0006-3363
Publication date 2012-06
Sub-type Article (original research)
DOI 10.1095/biolreprod.111.098475
Volume 86
Issue 6
Start page 190.1
End page 190.9
Total pages 9
Place of publication Madison, WI, United States
Publisher Society for the Study of Reproduction
Collection year 2013
Language eng
Formatted abstract
Human preterm and term parturition is associated with inflammatory cascades in the uteroplacental unit. Activation of the complement cascade releases potent proinflammatory mediators, including the anaphylatoxin C5a, which exerts its biological effects through its receptors, C5AR (also known as CD88) and C5L2, official symbol GPR77. To date, there are few data available on the role of C5a and CD88 in human pregnancy, so the aim of this study was to determine the effect of C5a and CD88 on some key inflammatory pathways involved in human parturition. Placental tissue samples were obtained from normal pregnancies at the time of Cesarean section. Human placental and fetal membranes were incubated in the absence (basal control) or presence of 0.5 μg/ml (∼60 nM) human recombinant C5a for 24 h. Concentrations of proinflammatory cytokines, prostaglandins, and 8-isoprostane (a marker of oxidative stress) were quantified by ELISA and secretory matrix metalloproteinases (MMPs) activity by zymography. NFKB DNA binding activity and NFKBIA (IkappaB-alpha; inhibitor of NFKB) protein degradation were analyzed by ELISA and Western blotting, respectively. In the presence of C5a, proinflammatory cytokines (IL6 and IL8), cyclooxygenase (COX)-2; official symbol PTGS2) expression, and subsequent prostaglandin (PGE2 and PGF2alpha), MMP9 enzyme production, and NFKB DNA activation were all significantly increased. The C5a-induced prolabor responses were significantly reduced by treatment with the selective CD88 antagonist PMX53 and the NFKB inhibitor BAY 11-7082. We conclude that C5a upregulates prolabor mediators in human gestational tissues via CD88-mediated NFKB activation.
Keyword C5a
Fetal membranes
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article # 190

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Biomedical Sciences Publications
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Citation counts: TR Web of Science Citation Count  Cited 8 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 9 times in Scopus Article | Citations
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Created: Mon, 27 Aug 2012, 12:59:24 EST by Dr Trent Woodruff on behalf of School of Biomedical Sciences