The Role Of Alarmins, Invariant Nkt Cells And Senescence In The Pathophysiology Of Sterile Intra-Amniotic Inflammation

THE ROLE OF ALARMINS, INVARIANT NKT CELLS AND SENESCENCE IN THEPATHOPHYSIOLOGY OF STERILE INTRA-AMNIOTIC INFLAMMATIONbyOLESYA PLAZYOAugust 2016Advisor: Nardhy Gomez-Lopez, Ph.D.Major: Physiology (Reproductive Sciences Concentration)Degree: Doctor of PhilosophyPreterm birth is defined as the delivery of a live baby prior to the 37th week ofgestation. It is the leading cause of neonatal mortality worldwide. Preterm neonatesare at a higher risk for shortand long-term complications, and prematurity placessignificant burden on our society. Elucidation of the mechanisms that lead tospontaneous preterm labor will enable development of therapies to prevent thissyndrome. We aimed to study pathological inflammation that is implicated in thepathophysiology of spontaneous preterm labor.Pathological inflammation can be initiated by the activation of innate immunityeither by microorganisms or alarmins, which are endogenous danger signals derivedcellular stress or injury. The inflammatory process initiated by alarmins in the amnioticcavity is referred to as sterile intraamniotic inflammation because it occurs in theabsence of detectable microbial infection. Sterile intra-amniotic inflammation is morecommon than microbial-associated intra-amniotic inflammation in patients with intactchorioamniotic membranes who undergo spontaneous preterm labor, andadministration of such alarmins as IL1α or HMGB1 was shown to induce preterm birth.