S100 calcium-binding protein A12 (S100A12)

S100 calcium-binding protein A12 (S100A12) is a member of the S100 family of EF-hand calcium-binding proteins, predominantly expressed and secreted by neutrophils and, to a lesser extent, by monocytes, some epithelial, and dendritic cells. S100A12 acts as a proinflammatory DAMP molecule: after secretion, it interacts primarily with the receptor for advanced glycation end products (RAGE), as well as toll-like receptor 4 (TLR4) and CD36, activating NF-κB and MAPK signaling pathways. This results in increased cytokine production, leukocyte adhesion and chemotaxis, and amplification of the inflammatory response. S100A12 possesses antibacterial and antifungal activities via metal ion sequestration and plays an important role in nutritional immunity. Clinically, S100A12 is associated with a wide spectrum of inflammatory, cardiovascular, renal, and gastrointestinal diseases, and is investigated as a biomarker for disease activity and prognosis. Direct therapeutic targeting is in early stages of development, with some research indicating that small molecules can inhibit the S100A12–RAGE interaction.

Other names

Calgranulin CEN-RAGEExtracellular newly identified RAGE-binding proteinMigration inhibitory factor-related protein 6MRP-6p6CAAF1CAGCNeutrophil S100 proteinCalcium-binding protein in amniotic fluid 1Protein S100-A12CGRPCalcitermin

Inhibition/disruption of the S100A12–RAGE axis (e.g., Tranilast acts by blocking S100A12 binding to RAGE, thereby reducing proinflammatory signaling)