S100A9 Human

S100 calcium-binding protein A9 (S100A9), also known as myeloid-related protein 14 (MRP14) or calgranulin B, is a member of the S100 family of proteins. These proteins are characterized by their two EF-hand calcium-binding motifs and are involved in the regulation of a variety of cellular processes, including cell cycle progression and differentiation . S100A9 is primarily expressed in myeloid cells and is known to form a heterodimer with S100A8, another member of the S100 family, to create the complex known as calprotectin .

The preparation of human recombinant S100A9 involves several steps to ensure the protein’s purity and functionality. Typically, the gene encoding S100A9 is cloned into an expression vector, which is then introduced into a suitable host cell, such as E. coli. The host cells are cultured under conditions that promote the expression of the recombinant protein. After expression, the protein is purified using techniques such as affinity chromatography, which exploits the protein’s affinity for specific ligands, and size-exclusion chromatography, which separates proteins based on their size .

S100A9 is known to interact with various receptors and molecules within the cell. One of its primary interactions is with Toll-like receptor 4 (TLR4), which plays a crucial role in the immune response. The binding of S100A9 to TLR4 can activate signaling pathways that lead to the production of pro-inflammatory cytokines . Additionally, S100A9 can bind to the receptor for advanced glycation end products (RAGE), which is involved in various pathological processes, including inflammation and cancer .

S100A9 also plays a role in the regulation of the enzyme NADPH oxidase, which is involved in the production of reactive oxygen species (ROS). This regulation is crucial for the immune response, as ROS are used by immune cells to kill pathogens . Furthermore, S100A9 has been shown to inhibit the differentiation of dendritic cells and macrophages, leading to the accumulation of myeloid-derived suppressor cells (MDSCs), which are involved in the suppression of the immune response in cancer .

Altered expression of S100A9 has been associated with various diseases, including cystic fibrosis, where its expression is increased . In the context of cancer, S100A9 has been implicated in the abnormal differentiation of myeloid cells within the tumor microenvironment, contributing to an immunosuppressive environment that allows the tumor to evade the immune system . Additionally, S100A9 is a useful biomarker for inflammatory diseases and has potential as a therapeutic target for conditions involving excessive inflammation .