Endothelial cells retain inflammatory memory through chromatin remodeling in a two-hit model of infection-induced inflammation
Daniel Gonsales Spíndola, Amber Bahr, Samantha Clark, Gabriel Pin de Jesus, Nina Martino, Anthony M. Lowery, Shuhan Lu, Andrew Seeman, Grace Martino, Giesse Albeche Duarte, Elijah Crosbourne, Peter Vincent, Guangchun Bai, Alejandro P. Adam, Katherine C. MacNamara, Ramon Bossardi Ramos
Abstract
We uncover that endothelial cells retain a form of inflammatory memory, driven by chromatin remodeling and sustained JunB activity. Using two-hit models in mice and human endothelial cells, we show that an initial inflammatory exposure primes the endothelium for exaggerated responses to future inflammation. This discovery reveals a new mechanism of chronic endothelial dysfunction and identifies JunB as a potential therapeutic target in postsepsis care.
Topics & Concepts
JUNBChromatin remodelingChromatinEpigeneticsInflammationBiologyProinflammatory cytokineCell biologyImmunologyTranscription factorEndothelial activationEndotheliumEndothelial stem cellPriming (agriculture)HistoneCancer researchCytokineGene knockdownTranscriptional regulationRegulation of gene expressionEndothelial dysfunctionMedicineImmune responses and vaccinationsImmune Response and Inflammationinterferon and immune responses