Toll-like receptors 2 and 4 and the cryopyrin inflammasome in normal pregnancy and pre-eclampsia.

Abstract

OBJECTIVE:

Pre-eclampsia involves a maternal inflammatory response that differs from both normal pregnancy and normotensive intrauterine growth restriction (IUGR). Our objective was to examine neutrophil Toll-like receptor (TLR), cryopyrin, nuclear factor-kappaB (NF-kappaB) subunit and interleukin-1beta (IL-1beta), and inflammatory cytokine profiles in women with pre-eclampsia or normotensive IUGR, as well as in normal pregnancy and non-pregnancy controls.

DESIGN AND METHOD:

A case-control study was performed. We examined the messenger RNA (mRNA) and protein expressions of TLR4 and TLR2, mRNA levels of cryopyrin, IL-1beta, NF-kappaB subunits p50 and p65, as well as maternal serum inflammatory cytokine profiles (IL-2, IL-6, tumour necrosis factor-alpha [TNF-alpha], interferon-gamma [IFN-gamma] and IL-10) in women with and without pre-eclampsia using real-time reverse transcription polymerase chain reactions, flow cytometry and multiplex immunoassays.

SETTING:

A single tertiary maternity hospital in Vancouver, Canada.

POPULATION:

Women with early-onset pre-eclampsia (<34 weeks of gestation, n = 25), women with late-onset pre-eclampsia (>or=34(+0) weeks of gestation, n = 25), women with normotensive IUGR (n = 25), women with normal pregnancy (n = 75) and non-pregnancy (n = 25) controls.

RESULTS:

Women with pre-eclampsia (as a single combined group of early- and late-onset, and particularly in women with early-onset pre-eclampsia) had increased TLR2 and TLR4 mRNA and protein expressions elevated cryopyrin, NF-kappaB subunit, and IL-1beta mRNA expression, and TNF-alpha:IL-10 and IL-6:IL-10 ratios compared with other groups.

CONCLUSIONS:

These data suggest that TLRs and cryopyrin may modulate the innate immune response of the maternal syndrome of pre-eclampsia, and might also trigger the differential inflammatory response existing between early onset pre-eclampsia and normotensive IUGR.

• Authors: F Xie, Y Hu, S E Turvey, L A Magee, R M Brunham, K-C Choi, M Krajden, P C K Leung, D M Money, D M Patrick, E Thomas, P von Dadelszen
• Journal: BJOG : an international journal of obstetrics and gynaecology (BJOG) Vol. 117 Issue 1 Pg. 99-108 (Jan 2010) ISSN: 1471-0528 [Electronic] England
• PMID: 20002372 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• Interleukins
• NF-kappa B
• NLR Family, Pyrin Domain-Containing 3 Protein
• NLRP3 protein, human
• RNA, Messenger
• Toll-Like Receptor 2
• Toll-Like Receptor 4

Topics

• Adult
• Carrier Proteins (metabolism)
• Case-Control Studies
• Female
• Fetal Growth Retardation (immunology)
• Humans
• Immunity, Innate
• Interleukins (metabolism)
• NF-kappa B (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein
• Neutrophils (metabolism)
• Pre-Eclampsia (immunology)
• Pregnancy
• RNA, Messenger (metabolism)
• Toll-Like Receptor 2 (metabolism)
• Toll-Like Receptor 4 (metabolism)
• Up-Regulation