Chemokine
Overview
Chemokines are a family of small cytokines, or signaling proteins secreted by cells. Their name is derived from their ability to induce directed chemotaxis in nearby responsive cells; they are chemotactic cytokines. Cytokine proteins are classified as all proteins less than 40 kilodaltons. Some chemokines are considered pro-inflammatory and can be induced during an immune response to recruit cells of the immune system to a site of infection, while others are considered homeostatic and are involved in controlling the migration of cells during normal processes of tissue maintenance or development. Homeostatic chemokines can be found in tissues under normal conditions and are involved in the regulation of cell migration during processes such as tissue maintenance, immune surveillance, and cell homing. Chemokines are found in all vertebrates, some viruses and some bacteria, but none have been described for other invertebrates. Chemokines have been classified into four main subfamilies: CXC, CC, CX3C and XC. All of these proteins exert their biological effects by interacting with G protein-linked transmembrane receptors called chemokine receptors, that are selectively found on the surfaces of their target cells.
Structure and Function
Chemokines are small proteins with a molecular weight of approximately 8-10 kDa. They are characterized by a conserved structure that includes four cysteine residues which form two disulfide bonds. The arrangement of these cysteine residues gives rise to the four chemokine subfamilies: CXC, CC, CX3C, and XC. The first two cysteines are adjacent in the CC and CXC chemokines, but separated by one and three amino acids, respectively, in the CX3C and XC chemokines.
Chemokines function by binding to specific G protein-coupled receptors on the surface of cells, triggering intracellular signaling pathways that result in cellular responses such as migration, proliferation, or secretion of other molecules. The specific response depends on the type of cell and the specific chemokine and receptor involved.
Chemokine Receptors
Chemokine receptors are a type of G protein-coupled receptor found on the surface of certain cells, which interact with a type of cytokine known as a chemokine. There have been 19 distinct chemokine receptors discovered in mammals, each having the characteristic 7-transmembrane layout of this receptor class. Chemokine receptors can bind one or more types of chemokines, and their activation leads to intracellular signaling pathways that coordinate various cellular responses.
Role in Immune Response
Chemokines play a crucial role in the regulation of immune cell trafficking and function. They are involved in the recruitment of immune cells to sites of infection and inflammation, as well as in the regulation of cell maturation and activation. For example, the chemokine CXCL8, also known as interleukin-8 (IL-8), is a potent attractant for neutrophils, helping to guide these immune cells to sites of bacterial infection.
Clinical Significance
Given their role in immune cell function and inflammation, chemokines and their receptors are attractive targets for therapeutic intervention in a variety of diseases, including autoimmune disorders, cancer, and infectious diseases. For example, the CCR5 antagonist maraviroc is used in the treatment of HIV/AIDS, as the virus uses this chemokine receptor to enter cells. Similarly, inhibitors of the chemokine CXCL12 (also known as stromal cell-derived factor 1, SDF-1) are being investigated for the treatment of cancer, as this chemokine is involved in the migration of cancer cells and the formation of metastases.