Periodic Reporting for period 1 - FIREALARM (Inflammatory signals of cell death)
Periodo di rendicontazione: 2023-01-01 al 2025-06-30
Inflammatory cell death orchestrates tissue homeostasis in response to infection and tissue malfunction. However, unresolved cell death is detrimental and leads to chronic inflammatory conditions such as metabolic disorders, neurodegenerative diseases, and cancer. A special type of programmed cell death, termed pyroptosis, triggers inflammation in a cell-autonomous and non-cell-autonomous fashion by releasing signals that alert bystander cells and the whole organism. These signals comprise cytokines such as interleukin (IL)-1beta and danger-associated molecular patterns (DAMPs). The immunogenicity of cell death is believed to correlate with their release. While the pro-inflammatory capacity of pyroptosis can be attributed to the release of IL-1 family proteins in many settings, sterile pathology independent of major cytokines has raised excitement. These observations suggest that yet undescribed endogenous intercellular signals contribute to sterile inflammatory conditions.
In this project, we aim to identify i) novel endogenous signaling molecule(s), released during pyroptosis that drive paracrine responses in bystander cells and the whole organism; ii) their activated signaling pathways; and iii) diagnostic and therapeutic value in sterile inflammatory conditions.
Our research is still ongoing, however, we are working on two manuscripts at the moment, describing the fractionation of pyroptotic molecules and their bioactivities, as well as novel proteoforms of inflammatory proteins.
Our research is still ongoing, however, we are working on two manuscripts at the moment, describing the fractionation of pyroptotic molecules and their bioactivities, as well as novel proteoforms of inflammatory proteins.
So far, our research has revealed one previously unknown protein with paracrine activity, and several proteolytic inflammatory proteforms that can predict disease trajectories in sterile inflammaotry conditions.