CXCL10

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Chemokine (C-X-C motif) ligand 10
PDB 1o7z EBI.jpg
PDB rendering based on 1o7z.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CXCL10 ; C7; IFI10; INP10; IP-10; SCYB10; crg-2; gIP-10; mob-1
External IDs OMIM147310 MGI1352450 HomoloGene1203 GeneCards: CXCL10 Gene
RNA expression pattern
PBB GE CXCL10 204533 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3627 15945
Ensembl ENSG00000169245 ENSMUSG00000034855
UniProt P02778 P17515
RefSeq (mRNA) NM_001565 NM_021274
RefSeq (protein) NP_001556 NP_067249
Location (UCSC) Chr 4:
76.94 – 76.94 Mb
Chr 5:
92.35 – 92.35 Mb
PubMed search [1] [2]

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[edit]

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

Function[edit]

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[edit]

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.

Clinical significance[edit]

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.[8][9] 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.[10] 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.[11]

References[edit]

  1. ^ a b 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". Proc. Natl. Acad. Sci. U.S.A. 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". Cytogenet. Cell Genet. 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". J. Immunol. 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". J. Exp. Med. 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. ^ 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". J. Infect. Dis. 194 (7): 895–903. doi:10.1086/507307. PMID 16960776. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ Falconer K, Askarieh G, Weis N, Hellstrand K, Alaeus A, Lagging M (July 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". Scand J Infect Dis 42 (11–12): 100824014139078. doi:10.3109/00365548.2010.498019. PMID 20608766. 

Further reading[edit]

  • Farber JM (1997). "Mig and IP-10: CXC chemokines that target lymphocytes". J. Leukoc. Biol. 61 (3): 246–57. PMID 9060447. 
  • Neville LF, Mathiak G, Bagasra O (1998). "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 Rev. 8 (3): 207–19. doi:10.1016/S1359-6101(97)00015-4. PMID 9462486.