The Role of Interleukin-1 Beta in Mediating LPS-Induced Reverse Transendothelial Migration of Intimal Dendritic Cells
Year: 2018
Type: dissertation
Abstract: Intimal dendritic-like cells (DCs) reside in regions of the aorta predisposed to atherosclerosis. LPS and interleukin-1 beta (IL-1β) injections into C57BL/6 mice result in decreased numbers of intimal DCs due to their exit into the blood via reverse transendothelial migration (RTM). This study evaluated the role of IL-1b in RTM induced by intravenous LPS injection. IL-1β mRNA expression was rapidly upregulated in the intima by LPS. Experiments using genetic approaches (Il1b-/-, Casp1-/- and Il1r1-/- mice) and function-blocking antibodies demonstrated a critical role for IL-1b production and signalling in LPS-induced RTM. Reciprocal bone marrow transplantation experiments revealed that IL-1β production and signalling only in the non- hematopoietic compartment, likely endothelium, was critical. Ex vivo studies showed that IL-1b could rescue RTM in the Il1b-/- aorta, implicating sustained intimal IL-1b signalling. These data suggest that intimal IL-1β production and signalling in endothelial cells is required for LPS- induced RTM of intimal DCs.
Source: TSpace (University of Toronto)
Author: Andrew Sunil Rajkumar
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2940163042