Placental vessels and the umbilical circulatory network function to carry oxygen and nutrients to the fetus. It is at this level that placental lesions such as villitis, obliterative vasculopathy, and thrombotic vasculopathy have been observed in association with fetal inflammatory response syndrome (FIRS) and cerebral palsy. We used human umbilical vein endothelial cells (HUVECs) as a model to study the regulation of inflammation and thrombosis in fetal vessels by microbial products. In this thesis we measured interleukin-8 (IL-8) and tissue factor (TF) expression by HUVECs treated with lipopolysaccharide (LPS), poly (I:C) (PIC), and peptidoglycan (PG). Our results show a profound induction of IL-8 by PIC, a TLR-3 ligand. We also show a moderate induction of tissue factor expression in PIC-treated HUVECs. These results show that HUVECs are exquisitely sensitive to PIC and suggests an important role for viral infection in umbilical vessel inflammation. We additionally treated HUVECs with dexamethasone (DEX), an anti-inflammatory steroid, and melatonin (MT), a pineal gland product with immunomodulatory and anti-oxidant properties. DEX reduced the level of both IL-8 and TF expression in PIC-treated cells. MT, however, further enhanced IL-8 expression in PIC-treated cells. Our results indicate a potential role for glucocorticoid therapy in reducing placental vessel inflammation and thrombosis. Thus, intervention with GC in pregnancies with FIRS may reduce the severity of placental lesions associated with cerebral palsy.
| Identifer | oai:union.ndltd.org:YALE_med/oai:ymtdl.med.yale.edu:etd-08072007-132134 |
| Date | 11 February 2008 |
| Creators | Davarya, Shekar Ligia |
| Contributors | Seth Guller |
| Publisher | Yale University |
| Source Sets | Yale Medical student MD Thesis |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://ymtdl.med.yale.edu/theses/available/etd-08072007-132134/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Yale School of Medicine or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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