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Title: The regulation of inflammatory mediators in human endometrium
Author: King, Anne Elizabeth
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2000
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NFkB pathway intermediates were identified in endometrium and decidua. The mRNA expression profiles of the inhibitory protein, IkBa, and an upstream kinase, TANK binding kinase 1, suggest that the pathway is activated during menstruation. Additionally, intermediates involved in the NFkB activating pathway are differentially regulated in the first trimester decidua. The pathway that mediates proinflammatory signaling (MEKK1-IKKb) to NFkB is downregulated in decidua consistent with the local immunosuppression which occurs during pregnancy. In contrast, intermediates involved in morphogenic signaling (NIK-IKKa) to NFkB are increased. This suggests a role in the expression of molecules crucial to successful pregnancy. The T47D cell line expresses high levels of progesterone receptor and was used as a cell model to study the effects of progesterone on the NFkB pathway. IkBa mRNA expression was found to be increased by progesterone while other pathway intermediates were unaffected by progesterone over the timecourse investigated. CD40 is a proinflammatory signaling molecule that activates NFkB. CD40 was detected in the perivascular region of endometrium. Previously, it has been reported that chemokine expression is upregulated in this region premenstrually and the detection of CD40 in this area suggests a role in the control of inflammatory mediator expression during menstruation. Messenger RNA expression for CD40 and its ligand, CD40L, was increased in decidua suggesting a role similar to that of NIK-IKKa. Secretory leukocyte protease inhibitor (SLPI) is an anti-inflammatory and antimicrobial molecule that also has inhibitory effects on the NFkB pathway. SLPI was localized to the glandular epithelium of endometrium from the mid-late secretory phase and was also detected in first trimester decidua. SLPI may provide antimicrobial protection at the time of implantation and during pregnancy. The detection of NFkB pathway intermediates, the CD40-CD40L system and SLPI in human endometrium supports a role for interfacing control mechanisms in the regulation of inflammatory mediators in the uterus.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available