ORIGINAL ARTICLE: Antiphospholipid Antibodies Limit Trophoblast Migration by Reducing IL-6 Production and STAT3 Activity
Article first published online: 3 FEB 2010
© 2010 John Wiley & Sons A/S
American Journal of Reproductive Immunology
Volume 63, Issue 5, pages 339–348, May 2010
How to Cite
Mulla, M. J., Myrtolli, K., Brosens, J. J., Chamley, L. W., Kwak-Kim, J. Y., Paidas, M. J. and Abrahams, V. M. (2010), ORIGINAL ARTICLE: Antiphospholipid Antibodies Limit Trophoblast Migration by Reducing IL-6 Production and STAT3 Activity. American Journal of Reproductive Immunology, 63: 339–348. doi: 10.1111/j.1600-0897.2009.00805.x
- Issue published online: 9 APR 2010
- Article first published online: 3 FEB 2010
- Submitted December 3, 2009; accepted December 7, 2009.
Vol. 65, Issue 1, 88, Article first published online: 9 DEC 2010
- Antiphospholipid syndrome;
- Interleukin 6;
- signal transducer and activator of transcription 3;
Citation Mulla MJ, Myrtolli K, Brosens JJ, Chamley LW, Kwak-Kim JY, Paidas MJ, Abrahams VM. Antiphospholipid antibodies limit trophoblast migration by reducing IL-6 production and STAT3 activity. Am J Reprod Immunol 2010
Women with antiphospholipid antibodies (aPL) are at risk of recurrent miscarriage and pre-eclampsia. aPL target the placenta by binding to β2-glycoprotein I (β2 GPI) expressed by the trophoblast. The objective of this study was to evaluate if and how aPL affect first trimester trophoblast migration.
Method of study
First trimester trophoblast cells were treated with anti-β2 GPI monoclonal antibodies. Migration was determined using a two-chamber assay. Interleukin (IL)-6 production was evaluated by RT-PCR and enzyme-linked immunosorbent assay, and signal transducer and activator of transcription 3 (STAT3) activation was assessed by western blot.
Trophoblast cells constitutively secreted IL-6 in a time-dependent manner and this directly correlated with STAT3 phosphorylation. In the presence of anti-β2 GPI Abs, trophoblast IL-6 mRNA levels and secretion was downregulated in a Toll-like receptor 4/MyD88-independent manner and this correlated with a reduction in phosphorylated STAT3 levels. In addition, the anti-β2 GPI Abs reduced the migratory potential of trophoblast. Heparin was able to reverse aPL-dependent inhibition of trophoblast IL-6 secretion and migration.
This study demonstrates that aPL limit trophoblast cell migration by downregulating trophoblast IL-6 secretion and STAT3 activity. As heparin was unable to prevent these effects, our findings may explain why women with antiphospholipid syndrome, treated with heparin, remain at risk of developing obstetrical syndromes, associated with impaired deep placentation, such as pre-eclampsia.