Representing the Process of Inflammation as Key Events in Adverse Outcome Pathways

Toxicological Sciences : an Official Journal of the Society of Toxicology
Daniel VilleneuveFlorianne Tschudi-Monnet

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 ...Continue Reading

Citations

Sep 12, 2019·Frontiers in Nutrition·Willem van den BrinkSuzan Wopereis
Aug 25, 2019·Archives of Toxicology·Nicoleta SpinuAndrew P Worth
Sep 26, 2020·Frontiers in Bioengineering and Biotechnology·Barbara DraslerBarbara Rothen-Rutishauser
Jan 1, 2020·BMC Pulmonary Medicine·Christian MonséThomas Brüning
Apr 15, 2020·Annual Review of Pharmacology and Toxicology·Hedwig M BraakhuisFlemming R Cassee
Dec 16, 2020·International Journal of Molecular Sciences·Isabel KarkossaKristin Schubert
Mar 7, 2021·International Journal of Molecular Sciences·Encarnación FusterMiguel A Sogorb
Jun 8, 2021·Frontiers in Public Health·Penny NymarkClemens Wittwehr
Jun 18, 2021·Journal of Inflammation Research·Rahnuma AhmadMainul Haque
Jan 11, 2022·The Science of the Total Environment·Kimberly A FinlaysonJason P van de Merwe
Jan 28, 2022·Alternatives to Laboratory Animals : ATLA·Brigitte Landesmann, Alicia Paini

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