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

  1. F Xie1,5,
  2. Y Hu1,5,
  3. SE Turvey2,7,
  4. LA Magee3,5,
  5. RM Brunham4,7,
  6. K-C Choi1,5,
  7. M Krajden4,7,
  8. PCK Leung1,5,
  9. DM Money1,7,
  10. DM Patrick4,7,
  11. E Thomas4,7,
  12. P von Dadelszen1,5

Article first published online: 10 DEC 2009

DOI: 10.1111/j.1471-0528.2009.02428.x

Issue

BJOG: An International Journal of Obstetrics & Gynaecology

BJOG: An International Journal of Obstetrics & Gynaecology

Volume 117, Issue 1, pages 99–108, January 2010

Additional Information

How to Cite

Xie, F., Hu, Y., Turvey, S., Magee, L., Brunham, R., Choi, K.-C., Krajden, M., Leung, P., Money, D., Patrick, D., Thomas, E. and von Dadelszen, P. (2010), Toll-like receptors 2 and 4 and the cryopyrin inflammasome in normal pregnancy and pre-eclampsia. BJOG: An International Journal of Obstetrics & Gynaecology, 117: 99–108. doi: 10.1111/j.1471-0528.2009.02428.x

Author Information

  1. 1

    Departments of Obstetrics and Gynaecology

  2. 2

    Pediatrics

  3. 3

    Medicine

  4. 4

    Pathology and Laboratory Medicine

  5. 5

    the CFRI Reproduction and Healthy Pregnancy Programme

  6. 7

    the UBC Centre for Disease Control, University of British Columbia, Vancouver, BC, Canada

*Dr P von Dadelszen, 2H30-4500 Oak Street, Vancouver, BC, Canada, V6H 3N1. Email pvd@cw.bc.ca

Publication History

  1. Issue published online: 10 DEC 2009
  2. Article first published online: 10 DEC 2009
  3. Accepted 26 September 2009.

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Keywords:

  • Cryopyrin;
  • cytokines;
  • pre-eclampsia;
  • toll-like receptor-2;
  • toll-like receptor-4

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-κB (NF-κB) subunit and interleukin-1β (IL-1β), 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-1β, NF-κB subunits p50 and p65, as well as maternal serum inflammatory cytokine profiles (IL-2, IL-6, tumour necrosis factor-α [TNF-α], interferon-γ [IFN-γ] 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 (≥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-κB subunit, and IL-1β mRNA expression, and TNF-α: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.

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