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

BJOG. 2010 Jan;117(1):99-108. doi: 10.1111/j.1471-0528.2009.02428.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • 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