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Updated: Mar 19, 2026

Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
Published on: September 15, 2017
[DAMPs (damage-associated molecular patterns) and inflammation]
Abstract:
Post-ischemic inflammation is re-appraised as an important player in the progression of ischemic stroke. Activation of inflammatory cells via Toll-like receptor 2 (TLR2) and TLR4 is caused by several damage-associated molecular patterns (DAMPs), including high mobility group box-1 (HMGB-1) and heat shock proteins. We have recently found that peroxiredoxin (Prx) is one of the strong DAMPs and activates infiltrating macrophages in brain ischemia. We have also found that interleukin-23 (IL-23) from the activated macrophages stimulates γδT cells which release IL-17, thereby causing the delayed expansion of infarct lesions. Further investigation of the innate immune response would lead to development of novel stroke treatment with a broad therapeutic time window.
Insights
Post-ischemic inflammation drives ischemic stroke progression. Damage-associated molecular patterns, like peroxiredoxin, activate immune cells, leading to delayed infarct expansion and suggesting new therapeutic targets.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Context:
- Ischemic stroke progression is significantly influenced by post-ischemic inflammation.
- Damage-associated molecular patterns (DAMPs) activate inflammatory cells through Toll-like receptors (TLR2 and TLR4).
- Key DAMPs include high mobility group box-1 (HMGB-1) and heat shock proteins.
Purpose:
- To investigate the role of peroxiredoxin (Prx) as a DAMP in brain ischemia.
- To elucidate the inflammatory cascade involving macrophages, IL-23, and γδT cells.
- To identify novel therapeutic targets for ischemic stroke treatment.
Summary:
- Peroxiredoxin (Prx) acts as a potent DAMP, activating infiltrating macrophages in the context of brain ischemia.
- Activated macrophages release interleukin-23 (IL-23), which stimulates γδT cells.
- These γδT cells subsequently release IL-17, contributing to delayed expansion of infarct lesions.
Impact:
- Highlights the critical role of the innate immune response in ischemic stroke pathogenesis.
- Suggests that targeting the Prx-macrophage-IL-23-γδT cell axis could offer novel therapeutic strategies.
- Presents potential for developing stroke treatments with a broader therapeutic time window.
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