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{{Infobox_gene}}
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'''C-X-C motif chemokine 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]].<ref name="pmid3925348">{{cite journal | vauthors = Luster AD, Unkeless JC, Ravetch JV | title = Gamma-interferon transcriptionally regulates an early-response gene containing homology to platelet proteins | journal = Nature | volume = 315 | issue = 6021 | pages = 672–6 | year = 1985 | pmid = 3925348 | doi = 10.1038/315672a0 }}</ref><ref name="pmid2437586">{{cite journal | vauthors = Luster AD, Jhanwar SC, Chaganti RS, Kersey JH, Ravetch JV | title = Interferon-inducible gene maps to a chromosomal band associated with a (4;11) translocation in acute leukemia cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 84 | issue = 9 | pages = 2868–71 | date = May 1987 | pmid = 2437586 | pmc = 304761 | doi = 10.1073/pnas.84.9.2868 }}</ref> C-X-C motif chemokine 10 is a small [[cytokine]] belonging to the CXC [[chemokine]] family.
{{GNF_Protein_box
| image = CXCL10.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1o7z.
| PDB = {{PDB2|1lv9}}, {{PDB2|1o7y}}, {{PDB2|1o7z}}, {{PDB2|1o80}}
| Name = Chemokine (C-X-C motif) ligand 10
| HGNCid = 10637
| Symbol = CXCL10
| AltSymbols =; C7; IFI10; INP10; IP-10; SCYB10; crg-2; gIP-10; mob-1
| OMIM = 147310
| ECnumber = 
| Homologene = 1203
| MGIid = 1352450
| GeneAtlas_image1 = PBB_GE_CXCL10_204533_at_tn.png
| Function = {{GNF_GO|id=GO:0008009 |text = chemokine activity}} {{GNF_GO|id=GO:0008603 |text = cAMP-dependent protein kinase regulator activity}}
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005615 |text = extracellular space}} {{GNF_GO|id=GO:0005625 |text = soluble fraction}}  
| Process = {{GNF_GO|id=GO:0006928 |text = cell motility}} {{GNF_GO|id=GO:0006935 |text = chemotaxis}} {{GNF_GO|id=GO:0006954 |text = inflammatory response}} {{GNF_GO|id=GO:0006955 |text = immune response}} {{GNF_GO|id=GO:0007166 |text = cell surface receptor linked signal transduction}} {{GNF_GO|id=GO:0007267 |text = cell-cell signaling}} {{GNF_GO|id=GO:0007517 |text = muscle development}} {{GNF_GO|id=GO:0008015 |text = circulation}} {{GNF_GO|id=GO:0008284 |text = positive regulation of cell proliferation}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 3627
    | Hs_Ensembl = ENSG00000169245
    | Hs_RefseqProtein = NP_001556
    | Hs_RefseqmRNA = NM_001565
    | Hs_GenLoc_db =
    | Hs_GenLoc_chr = 4
    | Hs_GenLoc_start = 77161297
    | Hs_GenLoc_end = 77163674
    | Hs_Uniprot = P02778
    | Mm_EntrezGene = 15945
    | Mm_Ensembl = ENSMUSG00000034855
    | Mm_RefseqmRNA = XM_975312
    | Mm_RefseqProtein = XP_980406
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 5
    | Mm_GenLoc_start = 93423001
    | Mm_GenLoc_end = 93424014
    | Mm_Uniprot = Q3U6X5
  }}
}}


'''Chemokine (C-X-C motif) ligand 10''' (CXCL10) or '''IP-10'''<ref>[http://www.ihop-net.org/UniPub/iHOP/gs/89508.html CXCL10 - chemokine (C-X-C motif) ligand 10]</ref> is a small [[cytokine]] belonging to the CXC [[chemokine]] family that is also known as 10 kDa interferon-gamma-induced protein (γ-IP10 or
== Gene ==
IP-10).  CXCL10 is secreted by several cell types in response to [[interferon#type II IFN|IFN-γ]]. These cell types include [[monocyte]]s, [[endothelial cell]]s and [[fibroblast]]s.<ref>Luster et al. Gamma-interferon transcriptionally regulates an early-response gene containing homology to platelet proteins. Nature 315: 672-676, 1985. PMID 3925348</ref> CXCL10 has been attributed to several roles, such as chemoattraction for [[monocyte]]s and [[T cell]]s, promotion of [[T cell]] adhesion to [[endothelial cell]]s, antitumor activity, and inhibition of [[bone marrow]] colony formation and [[angiogenesis]].<ref>Dufour et al. IFN-gamma-inducible protein 10 (IP-10; CXCL10) -deficient mice reveal a role for IP-10 in effector T cell generation and trafficking. J. Immun. 168:, 2002. PMID 11907072</ref><ref>Angiolillo et al. Human interferon-inducible protein 10 is a potent inhibitor of angiogenesis ''in vivo''. J. Exp. Med. 182: 155-162, 1995. PMID 7540647</ref>  The gene for CXCL10 is located on human [[chromosome 4]] in a cluster among several other CXC chemokines.<ref>O'Donovan et al. Physical mapping of the CXC chemokine locus on human chromosome 4. Cytogenet. Cell Genet. 84: 39-42, 1999. PMID 10343098</ref>  This chemokine elicits its effects by binding to the cell surface [[chemokine receptor]] [[CXCR3]].<ref>Booth et al. The CXCR3 binding chemokine IP-10/CXCL10: structure and receptor interactions. Biochemistry 41:, 2002. PMID 12173928</ref>. The three-dimensional crystal structure of this chemokine has been determined under 3 different conditions to a resolution of up to 1.92A.<ref>Swaminathan et al. Crystal structures of oligomeric forms of the IP-10/CXCL10 chemokine. Structure 11: 521-32, 2003. PMID 12737818</ref> The [[Protein Data Bank]] accession codes for the structures of CXCL10 are [http://www.ebi.ac.uk/msd-srv/msdlite/atlas/summary/1lv9.html 1lv9],[http://www.ebi.ac.uk/msd-srv/msdlite/atlas/summary/1o7y.html 1o7y],[http://www.ebi.ac.uk/msd-srv/msdlite/atlas/summary/1o7z.html 1o7z] and [http://www.ebi.ac.uk/msd-srv/msdlite/atlas/summary/1o80.html 1o80].


==References==
The gene for CXCL10 is located on human [[chromosome 4]] in a cluster among several other CXC chemokines.<ref name="pmid10343098">{{cite journal | vauthors = O'Donovan N, Galvin M, Morgan JG | title = Physical mapping of the CXC chemokine locus on human chromosome 4 | journal = Cytogenetics and Cell Genetics | volume = 84 | issue = 1-2 | pages = 39–42 | year = 1999 | pmid = 10343098 | doi = 10.1159/000015209 }}</ref>
{{reflist|2}}


==Further reading==
== Function ==
 
CXCL10 is secreted by several cell types in response to [[interferon#type II IFN|IFN-γ]]. These cell types include [[monocyte]]s, [[endothelial cell]]s and [[fibroblast]]s.<ref name="pmid3925348"/> CXCL10 has been attributed to several roles, such as chemoattraction for [[monocyte]]s/[[macrophage]]s, [[T cell]]s, [[NK cells]], and [[dendritic cells]],  promotion of [[T cell]] adhesion to [[endothelial cell]]s, antitumor activity, and inhibition of [[bone marrow]] colony formation and [[angiogenesis]].<ref name="pmid11907072">{{cite journal | vauthors = Dufour JH, Dziejman M, Liu MT, Leung JH, Lane TE, Luster AD | title = IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking | journal = Journal of Immunology | volume = 168 | issue = 7 | pages = 3195–204 | date = April 2002 | pmid = 11907072 | doi =  }}</ref><ref name="pmid7540647">{{cite journal | vauthors = Angiolillo AL, Sgadari C, Taub DD, Liao F, Farber JM, Maheshwari S, Kleinman HK, Reaman GH, Tosato G | title = Human interferon-inducible protein 10 is a potent inhibitor of angiogenesis in vivo | journal = The Journal of Experimental Medicine | volume = 182 | issue = 1 | pages = 155–62 | date = July 1995 | pmid = 7540647 | pmc = 2192108 | doi = 10.1084/jem.182.1.155 }}</ref>
 
This chemokine elicits its effects by binding to the cell surface [[chemokine receptor]] [[CXCR3]].<ref name="pmid12173928">{{cite journal | vauthors = Booth V, Keizer DW, Kamphuis MB, Clark-Lewis I, Sykes BD | title = The CXCR3 binding chemokine IP-10/CXCL10: structure and receptor interactions | journal = Biochemistry | volume = 41 | issue = 33 | pages = 10418–25 | date = August 2002 | pmid = 12173928 | doi = 10.1021/bi026020q }}</ref>
 
== 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.<ref name="pmid12737818">{{cite journal | vauthors = Swaminathan GJ, Holloway DE, Colvin RA, Campanella GK, Papageorgiou AC, Luster AD, Acharya KR | title = Crystal structures of oligomeric forms of the IP-10/CXCL10 chemokine | journal = Structure | volume = 11 | issue = 5 | pages = 521–32 | date = May 2003 | pmid = 12737818 | doi = 10.1016/S0969-2126(03)00070-4 }}</ref> The [[Protein Data Bank]] accession codes for the structures of CXCL10 are {{PDB2|1lv9}}, {{PDB2|1o7y}}, and {{PDB2|1o80}}.
 
== 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.<ref>{{cite journal | vauthors = Altara R, Gu YM, Struijker-Boudier HA, Thijs L, Staessen JA, Blankesteijn WM | title = Left Ventricular Dysfunction and CXCR3 Ligands in Hypertension: From Animal Experiments to a Population-Based Pilot Study | journal = PLoS One | volume = 10 | issue = 10 | pages = e0141394 | date = 2015 | doi = 10.1371/journal.pone.0141394 | pmid = 26506526 }}</ref>
<ref>{{cite journal | vauthors = Altara R, Manca M, Hessel MH, Gu Y, van Vark LC, Akkerhuis KM, Staessen JA, Struijker-Boudier HA, Booz GW, Blankesteijn WM | title = CXCL10 Is a Circulating Inflammatory Marker in Patients with Advanced Heart Failure: a Pilot Study | journal = Journal of Cardiovascular Translational Research | volume = 9 | issue = 4 | pages = 302–14 | date = August 2016 | doi = 10.1007/s12265-016-9703-3 | pmid = 27271043 }}</ref>
 
== 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.<ref name="pmid16960776">{{cite journal | vauthors = 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 | title = 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 | journal = The Journal of Infectious Diseases | volume = 194 | issue = 7 | pages = 895–903 | date = October 2006 | pmid = 16960776 | doi = 10.1086/507307 }}</ref><ref name="pmid17133471">{{cite journal | vauthors = 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 | title = IP-10 predicts viral response and therapeutic outcome in difficult-to-treat patients with HCV genotype 1 infection | journal = Hepatology | volume = 44 | issue = 6 | pages = 1617–25 | date = December 2006 | pmid = 17133471 | doi = 10.1002/hep.21407 }}</ref> 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.<ref name="pmid20186843">{{cite journal | vauthors = 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 | title = 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 | journal = Hepatology | volume = 51 | issue = 5 | pages = 1523–30 | date = May 2010 | pmid = 20186843 | doi = 10.1002/hep.23509 }}</ref> 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.<ref name="pmid20608766">{{cite journal | vauthors = Falconer K, Askarieh G, Weis N, Hellstrand K, Alaeus A, Lagging M | title = 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 | journal = Scandinavian Journal of Infectious Diseases | volume = 42 | issue = 11-12 | pages = 896–901 | date = December 2010 | pmid = 20608766 | doi = 10.3109/00365548.2010.498019 }}</ref>
 
== References ==
{{reflist}}
 
==External links==
* {{UCSC gene info|C7}}
* {{UCSC gene info|CXCL10}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Farber JM | title = Mig and IP-10: CXC chemokines that target lymphocytes | journal = Journal of Leukocyte Biology | volume = 61 | issue = 3 | pages = 246–57 | date = March 1997 | pmid = 9060447 | doi =  }}
| citations =
* {{cite journal | vauthors = Neville LF, Mathiak G, Bagasra O | title = The immunobiology of interferon-gamma inducible protein 10 kD (IP-10): a novel, pleiotropic member of the C-X-C chemokine superfamily | journal = Cytokine & Growth Factor Reviews | volume = 8 | issue = 3 | pages = 207–19 | date = September 1997 | pmid = 9462486 | doi = 10.1016/S1359-6101(97)00015-4 }}
*{{cite journal | author=Farber JM |title=Mig and IP-10: CXC chemokines that target lymphocytes. |journal=J. Leukoc. Biol. |volume=61 |issue= 3 |pages= 246-57 |year= 1997 |pmid= 9060447 |doi=  }}
*{{cite journal | author=Neville LF, Mathiak G, Bagasra O |title=The immunobiology of interferon-gamma inducible protein 10 kD (IP-10): a novel, pleiotropic member of the C-X-C chemokine superfamily. |journal=Cytokine Growth Factor Rev. |volume=8 |issue= 3 |pages= 207-19 |year= 1998 |pmid= 9462486 |doi= }}
}}
{{refend}}
{{refend}}


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Revision as of 14:25, 2 November 2017

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C-X-C motif chemokine 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][2] 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 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.[1] 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.[4][5]

This chemokine elicits its effects by binding to the cell surface chemokine receptor CXCR3.[6]

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.[7] The Protein Data Bank accession codes for the structures of CXCL10 are 1lv9​, 1o7y​, and 1o80​.

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.[8] [9]

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.[10][11] 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.[12] 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.[13]

References

  1. ↑ 1.0 1.1 Luster AD, Unkeless JC, Ravetch JV (1985). "Gamma-interferon transcriptionally regulates an early-response gene containing homology to platelet proteins". Nature. 315 (6021): 672–6. doi:10.1038/315672a0. PMID 3925348.
  2. ↑ Luster AD, Jhanwar SC, Chaganti RS, Kersey JH, Ravetch JV (May 1987). "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. doi:10.1073/pnas.84.9.2868. PMC 304761. PMID 2437586.
  3. ↑ O'Donovan N, Galvin M, Morgan JG (1999). "Physical mapping of the CXC chemokine locus on human chromosome 4". Cytogenetics and Cell Genetics. 84 (1–2): 39–42. doi:10.1159/000015209. PMID 10343098.
  4. ↑ Dufour JH, Dziejman M, Liu MT, Leung JH, Lane TE, Luster AD (April 2002). "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. PMID 11907072.
  5. ↑ Angiolillo AL, Sgadari C, Taub DD, Liao F, Farber JM, Maheshwari S, Kleinman HK, Reaman GH, Tosato G (July 1995). "Human interferon-inducible protein 10 is a potent inhibitor of angiogenesis in vivo". The Journal of Experimental Medicine. 182 (1): 155–62. doi:10.1084/jem.182.1.155. PMC 2192108. PMID 7540647.
  6. ↑ Booth V, Keizer DW, Kamphuis MB, Clark-Lewis I, Sykes BD (August 2002). "The CXCR3 binding chemokine IP-10/CXCL10: structure and receptor interactions". Biochemistry. 41 (33): 10418–25. doi:10.1021/bi026020q. PMID 12173928.
  7. ↑ Swaminathan GJ, Holloway DE, Colvin RA, Campanella GK, Papageorgiou AC, Luster AD, Acharya KR (May 2003). "Crystal structures of oligomeric forms of the IP-10/CXCL10 chemokine". Structure. 11 (5): 521–32. doi:10.1016/S0969-2126(03)00070-4. PMID 12737818.
  8. ↑ Altara R, Gu YM, Struijker-Boudier HA, Thijs L, Staessen JA, Blankesteijn WM (2015). "Left Ventricular Dysfunction and CXCR3 Ligands in Hypertension: From Animal Experiments to a Population-Based Pilot Study". PLoS One. 10 (10): e0141394. doi:10.1371/journal.pone.0141394. PMID 26506526.
  9. ↑ Altara R, Manca M, Hessel MH, Gu Y, van Vark LC, Akkerhuis KM, Staessen JA, Struijker-Boudier HA, Booz GW, Blankesteijn WM (August 2016). "CXCL10 Is a Circulating Inflammatory Marker in Patients with Advanced Heart Failure: a Pilot Study". Journal of Cardiovascular Translational Research. 9 (4): 302–14. doi:10.1007/s12265-016-9703-3. PMID 27271043.
  10. ↑ 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 (October 2006). "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. doi:10.1086/507307. PMID 16960776.
  11. ↑ 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 (December 2006). "IP-10 predicts viral response and therapeutic outcome in difficult-to-treat patients with HCV genotype 1 infection". Hepatology. 44 (6): 1617–25. doi:10.1002/hep.21407. PMID 17133471.
  12. ↑ 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 (May 2010). "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. doi:10.1002/hep.23509. PMID 20186843.
  13. ↑ Falconer K, Askarieh G, Weis N, Hellstrand K, Alaeus A, Lagging M (December 2010). "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. doi:10.3109/00365548.2010.498019. PMID 20608766.

External links

Further reading

  • Farber JM (March 1997). "Mig and IP-10: CXC chemokines that target lymphocytes". Journal of Leukocyte Biology. 61 (3): 246–57. PMID 9060447.
  • Neville LF, Mathiak G, Bagasra O (September 1997). "The immunobiology of interferon-gamma inducible protein 10 kD (IP-10): a novel, pleiotropic member of the C-X-C chemokine superfamily". Cytokine & Growth Factor Reviews. 8 (3): 207–19. doi:10.1016/S1359-6101(97)00015-4. PMID 9462486.
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