Abstract

Spontaneous preterm birth (PTB - Specific Aim 1 : To test the differences in the TH1/TH2 and proinflammatory cytokine/chemokine (IL-8) response and kinetics by normal human fetal membranes exposed to common intraamniotic pathogens including: Ureaplasma parvum, Mycoplasma hominis, E. coli, Group B Streptococcus, P. gingivalis and G. vaginalis.
Specific Aim 2 : To determine if there are racial differences in TH1/TH2 cytokine signature produced by fetal membranes in response to bacterial species listed above in Aim 1.
Specific Aim 3 : To test the anti-inflammatory properties of amniotic fluid in maintaining a balanced cytokine response.

Public Health Relevance

Microbial invasion of the intraamniotic cavity and intraamniotic infections and inflammation mediated by a switch in the TH1/TH2 cytokine pattern favoring a proinflammatory response are commonly associated with spontaneous preterm birth. Disproportionately higher rate of infection and preterm births in African Americans and increasing rate of infection associated preterm birth suggest that the infection associated pathophysiologic pathways and biomarkers may not be generalizable and each bacterium may produce their own inflammatory signature and racial disparity will be associated with biomarker profile. In this RO3 application, a pilot study is planned using an in vitro organ explant system for fetal membranes we plan to test differential inflammatory response and racial disparity associated with common intraamniotic pathogens.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
5R03HD067446-03
Application #
8239899
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Ilekis, John V
Project Start
2011-03-08
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2014-02-28
Support Year
3
Fiscal Year
2012
Total Cost
$81,800
Indirect Cost
$26,231

  Institution

Name
University of Texas Medical Br Galveston
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
800771149
City
Galveston
State
TX
Country
United States
Zip Code
77555

  Publications

Dixon, Christopher Luke; Richardson, Lauren; Sheller-Miller, Samantha et al. (2018) A distinct mechanism of senescence activation in amnion epithelial cells by infection, inflammation, and oxidative stress. Am J Reprod Immunol 79:
Menon, Ramkumar; Mesiano, Sam; Taylor, Robert N (2017) Programmed Fetal Membrane Senescence and Exosome-Mediated Signaling: A Mechanism Associated With Timing of Human Parturition. Front Endocrinol (Lausanne) 8:196
Bhat, Geeta; Peltier, Morgan R; Syed, Tariq Ali et al. (2013) Fetal membrane biomarker network diversity and disease functions induced by intra-amniotic pathogens. Am J Reprod Immunol 69:124-33
Abrahams, Vikki M; Potter, Julie A; Bhat, Geeta et al. (2013) Bacterial modulation of human fetal membrane Toll-like receptor expression. Am J Reprod Immunol 69:33-40
Peltier, Morgan R; Drobek, Cayce O; Bhat, Geeta et al. (2012) Amniotic fluid and maternal race influence responsiveness of fetal membranes to bacteria. J Reprod Immunol 96:68-78