Representing the Process of Inflammation as Key Events in Adverse Outcome Pathways.
Details
Serval ID
serval:BIB_6DD7C8C1C90C
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Representing the Process of Inflammation as Key Events in Adverse Outcome Pathways.
Journal
Toxicological sciences
ISSN
1096-0929 (Electronic)
ISSN-L
1096-0929
Publication state
Published
Issued date
01/06/2018
Peer-reviewed
Oui
Volume
163
Number
2
Pages
346-352
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review
Publication Status: ppublish
Publication Status: ppublish
Abstract
Inflammation is an important biological process involved in many target organ toxicities. However, there has been little consensus on how to represent inflammatory processes using the adverse outcome pathway (AOP) framework. In particular, there were concerns that inflammation was not being represented in a way that it would be recognized as a highly connected, central node within the global AOP network. The consideration of salient features common to the inflammatory process across tissues was used as a basis to propose 3 hub key events (KEs) for use in AOP network development. Each event, "tissue resident cell activation", "increased pro-inflammatory mediators", and "leukocyte recruitment/activation," is viewed as a hallmark of inflammation, independent of tissue, and can be independently measured. Using these proposed hub KEs, it was possible to link together a series of AOPs that previously had no shared KEs. Significant challenges remain with regard to accurate prediction of inflammation-related toxicological outcomes even if a broader and more connected network of inflammation-centered AOPs is developed. Nonetheless, the current proposal addresses one of the major hurdles associated with representation of inflammation in AOPs and may aid fit-for-purpose evaluations of other AOPs operating in a network context.
Keywords
Adverse Outcome Pathways, Alarmins/metabolism, Biomedical Research/methods, Biomedical Research/trends, Humans, Inflammation/metabolism, Inflammation Mediators/metabolism, Pathogen-Associated Molecular Pattern Molecules/metabolism
Pubmed
Web of science
Create date
15/06/2018 18:30
Last modification date
21/08/2019 6:15