Figure 4

Role of S100 protein in cell housekeeping and inflammation. S100 proteins are ubiquitously expressed in all cells and are crucial regulators of the calcium homeostasis machinery (1). The intracellular functions of S100 proteins also extend to specific cell functions such as transcriptional regulation and DNA repair (2), membrane protein recruitment and trafficking (3) and cytoskeleton assembly (4). The exact mechanisms that regulate the release of S100 proteins remain unclear thus far. Nevertheless, the secretion of S100 proteins occurs either passively upon cell damage or actively following cell activation (5). Once released into the extracellular space, S100 proteins interact with several receptors, most importantly RAGE and TLR4 (6). Upon binding to their receptors, S100 proteins trigger proinflammatory pathways promoting cell migration, proliferation and differentiation (7). S100 protein-induced signaling pathways also lead to the expression of MMPs and CAMs, thereby promoting chemotaxis and tissue remodeling (8). Certain S100 proteins, such as S100A8/A9, are extremely sensitive to oxidation (9). Their redox state acts as a molecular switch from proinflammatory function to protective wound-healing and antioxidant function. In return, oxidation-sensitive S100 proteins are believed to act as scavengers of ROS and NO and thereby prevent oxidative stress. CAM, cell adhesion molecule; MMP, matrix metalloproteinase; NO, nitric oxide; RAGE, receptor for advanced glycation end-products; ROS, reactive oxygen species; TLR4, Toll-like receptor 4.