Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

ORIGINAL ARTICLE : Antiphospholipid antibodies induce a pro-inflammatory response in first trimester trophoblast via the TLR4/MyD88 pathway

Tools
- Tools
+ Tools

Mulla, Melissa J., Brosens, Jan J., Chamley, Larry W., Giles, Ian, Pericleous, Charis, Rahman, Anisur, Joyce, Shawna K., Panda, Britta, Paidas, Michael J. and Abrahams, Vikki M. (2009) ORIGINAL ARTICLE : Antiphospholipid antibodies induce a pro-inflammatory response in first trimester trophoblast via the TLR4/MyD88 pathway. American Journal of Reproductive Immunology, Vol.62 (No.2). pp. 96-111. doi:10.1111/j.1600-0897.2009.00717.x ISSN 10467408.

Research output not available from this repository.

Request-a-Copy directly from author or use local Library Get it For Me service.

Official URL: http://dx.doi.org/10.1111/j.1600-0897.2009.00717.x

Request Changes to record.

Abstract

Problem  Women with antiphospholipid antibodies (aPL) are at risk for recurrent miscarriage, pre-eclampsia, and pre-term labor. aPL target the placenta directly by binding to beta2-glycoprotein I (β2GPI) expressed on the surface of trophoblast cells. The objective of this study was to determine the effects of aPL on trophoblast function and the mechanisms involved.

Method of study  First trimester trophoblast cells were treated with anti-β2GPI monoclonal antibodies and patient-derived aPL, after which cell survival and function was evaluated.

Results  We report that anti-β2GPI antibodies trigger an inflammatory response in trophoblast, characterized by increased secretion of interleukin (IL)-8, MCP-1, GRO-α, and IL-1β, and that this occurs in a TLR-4/MyD88-dependent manner. At high concentrations, these antibodies also induce caspase-mediated cell death. This was attenuated upon disabling of the MyD88 pathway, suggesting that anti-β2GPI-induced inflammatory mediators compromise trophoblast survival by acting in an autocrine/paracrine manner. Enhanced IL-8, GRO-α, and IL-1β secretion also occurred when trophoblast cells were incubated with antibodies from patients with antiphospholipid syndrome. Heparin, which acts as a pro-survival factor in human trophoblast, attenuated the anti-β2GPI antibody-mediated cell death, and also the pro-inflammatory response, but only at high concentrations.

Conclusion  These findings demonstrate that aPL triggers a placental inflammatory response via the TLR-4/MyD88 pathway, which in turn compromises trophoblast survival. Thus, the TLR-4/MyD88 pathway may provide a new therapeutic target to improve pregnancy outcome in antiphospholipid syndrome patients.

Item Type: Journal Article
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Reproductive Health ( - until July 2016)
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Journal or Publication Title: American Journal of Reproductive Immunology
Publisher: Wiley-Blackwell Publishing, Inc.
ISSN: 10467408
Official Date: August 2009
Dates:
DateEvent
August 2009Published
Volume: Vol.62
Number: No.2
Page Range: pp. 96-111
DOI: 10.1111/j.1600-0897.2009.00717.x
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item
twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us