OR6-001 - S100A12 as pro-inflammatory TLR4 ligand

Excerpt

The granulocyte-specific Ca²⁺-binding protein S100A12 is overexpressed during autoinflammation as well as other inflammatory conditions in humans and has been ascribed to the group of pro-inflammatory Damage Associated Molecular Pattern molecules (DAMPs). S100A12-levels in human serum reveal excellent correlation with patients’ inflammation state, which renders S100A12 a powerful biomarker. In order to operate as DAMP S100A12 requires binding to cellular receptors. The protein was originally found to bind RAGE and was in turn entitled extracellular newly identified RAGE-binding protein (EN-RAGE). RAGE ligation by S100A12 is proposed to trigger a pro-inflammatory cascade in microvascular endothelial cells, macrophages and lymphocytes, culminating in NFκ-B activation. This amplifies the inflammatory response by triggering further RAGE expression and thus drives a feed-forward loop that can potentiate inflammation. …