CXCL10 explained

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.[1] C-X-C motif chemokine 10 is a small cytokine belonging to the CXC chemokine family.

Gene

The gene for CXCL10 is located on human chromosome 4[2] in a cluster among several other CXC chemokines.[3]

Function

CXCL10 is secreted by several cell types in response to IFN-γ. These cell types include monocytes, endothelial cells and fibroblasts.[4] 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.[5] [6]

This chemokine elicits its effects by binding to the cell surface chemokine receptor CXCR3.[7]

Structure

The three-dimensional crystal structure of this chemokine has been determined under 3 different conditions to a resolution of up to 1.92 Å.[8] The Protein Data Bank accession codes for the structures of CXCL10 are,, and .

Biomarkers

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.[9] [10]

Clinical significance

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.[11] [12] 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.[13] 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.[14] The pathogen Leishmania major utilizes a protease, GP63, that cleaves CXCL10, implicating CXCL10 in host defense mechanisms of certain intracellular pathogens like Leishmania.[15]

Further reading

Notes and References

  1. Luster AD, Jhanwar SC, Chaganti RS, Kersey JH, Ravetch JV . Interferon-inducible gene maps to a chromosomal band associated with a (4;11) translocation in acute leukemia cells . Proceedings of the National Academy of Sciences of the United States of America . 84 . 9 . 2868–71 . May 1987 . 2437586 . 304761 . 10.1073/pnas.84.9.2868 . 1987PNAS...84.2868L . free .
  2. Web site: CXCL10 C-X-C motif chemokine ligand 10 [Homo sapiens (Human)] - Gene - NCBI .
  3. O'Donovan N, Galvin M, Morgan JG . Physical mapping of the CXC chemokine locus on human chromosome 4 . Cytogenetics and Cell Genetics . 84 . 1–2 . 39–42 . 1999 . 10343098 . 10.1159/000015209 . 8087808 .
  4. Luster AD, Unkeless JC, Ravetch JV . Gamma-interferon transcriptionally regulates an early-response gene containing homology to platelet proteins . Nature . 315 . 6021 . 672–6 . 1985 . 3925348 . 10.1038/315672a0 . 1985Natur.315..672L . 4358066 .
  5. Dufour JH, Dziejman M, Liu MT, Leung JH, Lane TE, Luster AD . IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking . Journal of Immunology . 168 . 7 . 3195–204 . April 2002 . 11907072 . 10.4049/jimmunol.168.7.3195 . free .
  6. Angiolillo AL, Sgadari C, Taub DD, Liao F, Farber JM, Maheshwari S, Kleinman HK, Reaman GH, Tosato G . 6 . Human interferon-inducible protein 10 is a potent inhibitor of angiogenesis in vivo . The Journal of Experimental Medicine . 182 . 1 . 155–62 . July 1995 . 7540647 . 2192108 . 10.1084/jem.182.1.155 .
  7. Booth V, Keizer DW, Kamphuis MB, Clark-Lewis I, Sykes BD . The CXCR3 binding chemokine IP-10/CXCL10: structure and receptor interactions . Biochemistry . 41 . 33 . 10418–25 . August 2002 . 12173928 . 10.1021/bi026020q .
  8. Swaminathan GJ, Holloway DE, Colvin RA, Campanella GK, Papageorgiou AC, Luster AD, Acharya KR . Crystal structures of oligomeric forms of the IP-10/CXCL10 chemokine . Structure . 11 . 5 . 521–32 . May 2003 . 12737818 . 10.1016/S0969-2126(03)00070-4 . free .
  9. Altara R, Gu YM, Struijker-Boudier HA, Thijs L, Staessen JA, Blankesteijn WM . Left Ventricular Dysfunction and CXCR3 Ligands in Hypertension: From Animal Experiments to a Population-Based Pilot Study . PLOS ONE . 10 . 10 . e0141394 . 2015 . 26506526 . 4624781 . 10.1371/journal.pone.0141394 . 2015PLoSO..1041394A . free .
  10. Altara R, Manca M, Hessel MH, Gu Y, van Vark LC, Akkerhuis KM, Staessen JA, Struijker-Boudier HA, Booz GW, Blankesteijn WM . 6 . CXCL10 Is a Circulating Inflammatory Marker in Patients with Advanced Heart Failure: a Pilot Study . Journal of Cardiovascular Translational Research . 9 . 4 . 302–14 . August 2016 . 27271043 . 10.1007/s12265-016-9703-3 . 41188765 .
  11. Romero AI, Lagging M, Westin J, Dhillon AP, Dustin LB, Pawlotsky JM, Neumann AU, Ferrari C, Missale G, Haagmans BL, Schalm SW, Zeuzem S, Negro F, Verheij-Hart E, Hellstrand K . 6 . Interferon (IFN)-gamma-inducible protein-10: association with histological results, viral kinetics, and outcome during treatment with pegylated IFN-alpha 2a and ribavirin for chronic hepatitis C virus infection . The Journal of Infectious Diseases . 194 . 7 . 895–903 . October 2006 . 16960776 . 10.1086/507307 . free .
  12. Lagging M, Romero AI, Westin J, Norkrans G, Dhillon AP, Pawlotsky JM, Zeuzem S, von Wagner M, Negro F, Schalm SW, Haagmans BL, Ferrari C, Missale G, Neumann AU, Verheij-Hart E, Hellstrand K . 6 . IP-10 predicts viral response and therapeutic outcome in difficult-to-treat patients with HCV genotype 1 infection . Hepatology . 44 . 6 . 1617–25 . December 2006 . 17133471 . 10.1002/hep.21407 . 27733803 . free .
  13. Askarieh G, Alsiö A, Pugnale P, Negro F, Ferrari C, Neumann AU, Pawlotsky JM, Schalm SW, Zeuzem S, Norkrans G, Westin J, Söderholm J, Hellstrand K, Lagging M . 6 . Systemic and intrahepatic interferon-gamma-inducible protein 10 kDa predicts the first-phase decline in hepatitis C virus RNA and overall viral response to therapy in chronic hepatitis C . Hepatology . 51 . 5 . 1523–30 . May 2010 . 20186843 . 10.1002/hep.23509 . 205873437 . free .
  14. Falconer K, Askarieh G, Weis N, Hellstrand K, Alaeus A, Lagging M . IP-10 predicts the first phase decline of HCV RNA and overall viral response to therapy in patients co-infected with chronic hepatitis C virus infection and HIV . Scandinavian Journal of Infectious Diseases . 42 . 11–12 . 896–901 . December 2010 . 20608766 . 10.3109/00365548.2010.498019 . 28542340 .
  15. Antonia AL, Gibbs KD, Trahair ED, Pittman KJ, Martin AT, Schott BH, Smith JS, Rajagopal S, Thompson JW, Reinhardt RL, Ko DC . 6 . Pathogen Evasion of Chemokine Response Through Suppression of CXCL10 . Frontiers in Cellular and Infection Microbiology . 9 . 280 . 2019 . 31440475 . 6693555 . 10.3389/fcimb.2019.00280 . free .

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