For Inflammation Research, S100A12 is all the RAGE

Tue, 04/24/2012 - 09:28

S100A12 (Calgranulin C) belongs to the S100 family of calcium-binding proteins. The 20 members of this group share EF-hand domains which are involved in binding of calcium. S100A12 is expressed by granulocytes, whereas its expression by monocytes remains controversial (1). S100A12 is secreted by activated granulocytes (2). S100A12 is a ligand for the receptor for advanced glycation end products (RAGE) expressed on macrophages, lymphocytes and endothelium. RAGE mediates an up-regulation of the connective tissue growth factor IGFBP-rP2 (insulin-like growth factor binding protein-related protein 2), which is a potent inducer of angiogenesis (3).

Western Blot: S100A12 Antibody

Additionally, RAGE has been shown to increase adhesion of granulocytes to stimulated endothelial cells (4). S100A12 serum levels might serve as a marker for local disease activity in different forms of arthritis as well. Patients with active arthritis revealed significantly higher S100A12 levels than healthy controls. The high local expression of S100A12 at the site of inflammation seems to be responsible for the correlating levels that are detected in serum (5). In different mouse models of inflammation including arthritis, blocking this interaction with soluble RAGE (sRAGE) and anti-S100A12 antibodies revealed clear anti-inflammatory effects (6). Further studies on the functional role of S100A12 in human arthritis have to prove the usefulness of new biological therapies that focus on pro-inflammatory activities of human S100A12. The expression of S100A12 in human arthritis provokes the question whether S100A12 protein and its interaction with RAGE might be a target for novel therapies.

  1. PMID: 10399917, 10973813
  2. PMID: 10726775
  3. PMID: 11316739
  4. PMID: 11854121
  5. PMID: 14644132
  6. PMID: 11581294

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