IDM Events

IDM Departmental Calendar

Event Category
Fri 9/20/2019 8:30AM - 12:00PM
35th Anniversary of the Pitt Men's Study IDM Event
35th Anniversary of the Pitt Men's Study
Fri 9/20/2019 8:30AM - 12:00PM
Public Health Auditorium (G23)


Public Health Auditorium (G23)
IDM
Event
Tue 10/8/2019 9:00AM - 4:30PM
PrEP Summit: Engagement, Adherence, Retention MidAtlantic AIDS Education and Training Center Conference
PrEP Summit: Engagement, Adherence, Retention
Tue 10/8/2019 9:00AM - 4:30PM
Outside Conference and Meeting Spaces


Outside Conference and Meeting Spaces
MidAtlantic AIDS Education and Training Center
Conference
Tue 10/22/2019 5:00PM - 8:30PM
Erie Evening Update: Sexual Health and Stigma MidAtlantic AIDS Education and Training Center Conference
Erie Evening Update: Sexual Health and Stigma
Tue 10/22/2019 5:00PM - 8:30PM
Outside Conference and Meeting Spaces

This evening dinner update, in collaboration with the Erie Department of Health and Erie HIV Task Force, will be held at the Bayfront Convention Center.  The presenters will discuss Sexual Health History Taking and Sexual Health and Stigma, followed by a panel of local providers.


Outside Conference and Meeting Spaces
MidAtlantic AIDS Education and Training Center
Conference

Recent Events

IDM Master's Defense

Bethany Flage - MS '18: Heme-induced acute lung injury by inflammasome activation in vascular...

Tuesday 4/17 11:00AM - 1:00PM
Public Health Lecture Hall (A115)

Heme-induced acute lung injury by inflammasome activation in vascular endothelium

Abstract: Acute lung injury (ALI) is a form of acute respiratory failure, having an estimated annual incidence of 200,000 with a 40% mortality rate in the United States alone. Patients suffering from hemolytic diseases such as sepsis, malaria, and sickle cell disease are placed at a greater risk of developing ALI because of the excess amount of heme release that occurs during the pathogenesis of these diseases. Free heme is known to be a danger associated molecular pattern (DAMP) molecule and previous reports from our lab have identified particularly toxic effects apply to the lung endothelial barrier, ultimately contributing to ALI. However, the cellular mechanism of how heme is able to cause endothelial damage remains largely unknown. Recent studies have revealed that heme is able to induce the activation of nod-like receptor 3 (NLRP3) inflammasome in monocytes, which is followed by the maturation and release of inflammatory molecules Interleukin-1 (IL-1) and Interleukin-18 (IL-18). Therefore, in this study we hypothesized that heme induces NLRP3 in pulmonary microvascular endothelial cells, resulting in destructive inflammatory activity that leads to the development of ALI. To test this hypothesis, we challenged human primary microvascular endothelial cells (HMVEC-Ls) with heme and assessed cell death, barrier integrity, cytokine release, and corresponding inflammasome activation. Heme challenge of HMVEC-Ls produced a 75% decrease in barrier resistance as compared to vehicle, measured via electrical cell-substrate impedance sensing (ECIS). This barrier instability was concomitant with a significant 3-fold increase in IL-18 (p=0.046) release and an increase in NLRP3 protein, measured through extracellular supernatant and western blot respectively. Importantly, inhibition of NLRP3 resulted in a 35% increase in barrier integrity, which corresponded to a 20% decrease in lung wet-to-dry weight ratio in mice that were injected with heme. These results demonstrate that heme mediated endothelial damage involves an inflammatory response associated with NLRP3 inflammasome activation, which is a potential target for therapeutic intervention. Future studies are warranted to confirm heme-mediated inflammasome formation and activation. Identifying specific molecular and cellular mechanisms by which heme damages the vascular endothelium in the pathogenesis of ALI is important for decreasing morbidity among patients and improving the overall health of the public. 

Advisor: Dr. Robbie Mailliard

Last Updated On Tuesday, April 17, 2018 by Abby Kincaid
Created On Tuesday, April 17, 2018

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