C-X-C motif chemokine ligand 10 (CXCL10) also known as Interferon gamma-induced protein 10 (IP-10) or small-inducible cytokine B10 is an 8.7 kDa protein that in humans is encoded by the CXCL10 gene. [5] [6] C-X-C motif chemokine 10 is a small cytokine belonging to the CXC chemokine family.
The gene for CXCL10 is located on human chromosome 4 [7] in a cluster among several other CXC chemokines. [8]
CXCL10 is secreted by several cell types in response to IFN-γ. These cell types include monocytes, endothelial cells and fibroblasts. [5] CXCL10 has been attributed to several roles, such as chemoattraction for monocytes/macrophages, T cells, NK cells, and dendritic cells, promotion of T cell adhesion to endothelial cells, antitumor activity, and inhibition of bone marrow colony formation and angiogenesis. [9] [10]
This chemokine elicits its effects by binding to the cell surface chemokine receptor CXCR3. [11]
The three-dimensional crystal structure of this chemokine has been determined under 3 different conditions to a resolution of up to 1.92 Å. [12] The Protein Data Bank accession codes for the structures of CXCL10 are 1lv9 , 1o7y , and 1o80 .
CXCL9, CXCL10 and CXCL11 have proven to be valid biomarkers for the development of heart failure and left ventricular dysfunction, suggesting an underlining pathophysiological relation between levels of these chemokines and the development of adverse cardiac remodeling. [13] [14]
Baseline pre-treatment plasma levels of CXCL10 are elevated in patients chronically infected with hepatitis C virus (HCV) of genotypes 1 or 4 who do not achieve a sustained viral response (SVR) after completion of antiviral therapy. [15] [16] CXCL10 in plasma is mirrored by intrahepatic CXCL10 mRNA, and both strikingly predict the first days of elimination of HCV RNA (“first phase decline”) during interferon/ribavirin therapy for all HCV genotypes. [17] This also applies for patients co-infected with HIV, where pre-treatment IP-10 levels below 150 pg/mL are predictive of a favorable response, and may thus be useful in encouraging these otherwise difficult-to-treat patients to initiate therapy. [18] The pathogen Leishmaniamajor utilizes a protease, GP63, that cleaves CXCL10, implicating CXCL10 in host defense mechanisms of certain intracellular pathogens like Leishmania. [19]
Interferons are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten their anti-viral defenses.
Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock as a product of human leukocytes stimulated with phytohemagglutinin, and by others as a product of antigen-stimulated lymphocytes. It was also shown to be produced in human lymphocytes. or tuberculin-sensitized mouse peritoneal lymphocytes challenged with Mantoux test (PPD); the resulting supernatants were shown to inhibit growth of vesicular stomatitis virus. Those reports also contained the basic observation underlying the now widely employed IFN-γ release assay used to test for tuberculosis. In humans, the IFN-γ protein is encoded by the IFNG gene.
Interleukin-29 (IL-29) is a cytokine and it belongs to type III interferons group, also termed interferons λ (IFN-λ). IL-29 plays an important role in the immune response against pathogenes and especially against viruses by mechanisms similar to type I interferons, but targeting primarily cells of epithelial origin and hepatocytes.
Chemokine ligand 9 (CXCL9) is a small cytokine belonging to the CXC chemokine family that is also known as monokine induced by gamma interferon (MIG). The CXCL9 is one of the chemokine which plays role to induce chemotaxis, promote differentiation and multiplication of leukocytes, and cause tissue extravasation.
C-X-C motif chemokine 11 (CXCL11) is a protein that in humans is encoded by the CXCL11 gene.
C-X-C motif chemokine 5 is a protein that in humans is encoded by the CXCL5 gene.
CXC chemokine receptors are integral membrane proteins that specifically bind and respond to cytokines of the CXC chemokine family. They represent one subfamily of chemokine receptors, a large family of G protein-linked receptors that are known as seven transmembrane (7-TM) proteins, since they span the cell membrane seven times. There are currently six known CXC chemokine receptors in mammals, named CXCR1 through CXCR6.
Chemokine receptor CXCR3 is a Gαi protein-coupled receptor in the CXC chemokine receptor family. Other names for CXCR3 are G protein-coupled receptor 9 (GPR9) and CD183. There are three isoforms of CXCR3 in humans: CXCR3-A, CXCR3-B and chemokine receptor 3-alternative (CXCR3-alt). CXCR3-A binds to the CXC chemokines CXCL9 (MIG), CXCL10 (IP-10), and CXCL11 (I-TAC) whereas CXCR3-B can also bind to CXCL4 in addition to CXCL9, CXCL10, and CXCL11.
Signal transducer and activator of transcription 1 (STAT1) is a transcription factor which in humans is encoded by the STAT1 gene. It is a member of the STAT protein family.
Interferon-stimulated gene 15 (ISG15) is a 17 kDA secreted protein that in humans is encoded by the ISG15 gene. ISG15 is induced by type I interferon (IFN) and serves many functions, acting both as an extracellular cytokine and an intracellular protein modifier. The precise functions are diverse and vary among species but include potentiation of Interferon gamma (IFN-II) production in lymphocytes, ubiquitin-like conjugation to newly-synthesized proteins and negative regulation of the IFN-I response.
RIG-I is a cytosolic pattern recognition receptor (PRR) that can mediate induction of a type-I interferon (IFN1) response. RIG-I is an essential molecule in the innate immune system for recognizing cells that have been infected with a virus. These viruses can include West Nile virus, Japanese Encephalitis virus, influenza A, Sendai virus, flavivirus, and coronaviruses.
Interferon alpha-1 is a protein that in humans is encoded by the IFNA1 gene.
Interferon beta is a protein that in humans is encoded by the IFNB1 gene. The natural and recombinant protein forms have antiviral, antibacterial, and anticancer properties.
Interferon alpha-2 is a protein that in humans is encoded by the IFNA2 gene.
Fibrinogen-like protein 2, also known as FGL2, is a protein which in humans is encoded by the FGL2 gene.
Interferon alfa (INN) or HuIFN-alpha-Le, trade name Multiferon, is a pharmaceutical drug composed of natural interferon alpha (IFN-α), obtained from the leukocyte fraction of human blood following induction with Sendai virus. Interferon alfa contains several naturally occurring IFN-α subtypes and is purified by affinity chromatography. Although the pharmaceutical product is often simply called "interferon alpha" or "IFN-α" like its endogenous counterpart, the product's International nonproprietary name (INN) is interferon alfa.
A hepatitis C vaccine, a vaccine capable of protecting against the hepatitis C virus (HCV), is not yet available. Although vaccines exist for hepatitis A and hepatitis B, development of an HCV vaccine has presented challenges. No vaccine is currently available, but several vaccines are currently under development.
Radical S-adenosyl methionine domain-containing protein 2 is a protein that in humans is encoded by the RSAD2 gene. RSAD2 is a multifunctional protein in viral processes that is an interferon stimulated gene. It has been reported that viperin could be induced by either IFN-dependent or IFN-independent pathways and certain viruses may use viperin to increase their infectivity.
Interferon lambda 3 encodes the IFNL3 protein. IFNL3 was formerly named IL28B, but the Human Genome Organization Gene Nomenclature Committee renamed this gene in 2013 while assigning a name to the then newly discovered IFNL4 gene. Together with IFNL1 and IFNL2, these genes lie in a cluster on chromosomal region 19q13. IFNL3 shares ~96% amino-acid identity with IFNL2, ~80% identity with IFNL1 and ~30% identity with IFNL4.
Interferon lambda 4 is one of the most recently discovered human genes and the newest addition to the interferon lambda protein family. This gene encodes the IFNL4 protein, which is involved in immune response to viral infection.
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