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CXCL1

From Wikipedia, the free encyclopedia
CXCL1
Available structures
PDBOrtholog search:PDBeRCSB
Identifiers
AliasesCXCL1,FSP, GRO1, GROa, MGSA, MGSA-a, NAP-3, SCYB1, C-X-C motif chemokine ligand 1
External IDsOMIM:155730;MGI:1340094;HomoloGene:136748;GeneCards:CXCL1;OMA:CXCL1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

2919

20310

Ensembl

ENSG00000163739

ENSMUSG00000058427

UniProt

P09341

P10889

RefSeq (mRNA)

NM_001511

NM_009140

RefSeq (protein)

NP_001502

NP_033166

Location (UCSC)Chr 4: 73.87 – 73.87 MbChr 5: 91.05 – 91.05 Mb
PubMedsearch[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Thechemokine (C-X-C motif) ligand 1(CXCL1) is a small peptide belonging to the CXCchemokinefamily that acts as a chemoattractant for several immune cells, especiallyneutrophils[5][6]or other non-hematopoietic cells to the site of injury or infection and plays an important role in regulation of immune and inflammatory responses. It was previously called GRO1 oncogene, GROα, neutrophil-activating protein 3 (NAP-3) and melanoma growth stimulating activity, alpha (MGSA-α). CXCL1 was first cloned from a cDNA library of genes induced by platelet-derived growth factor (PDGF) stimulation of BALB/c-3T3 murine embryonic fibroblasts and named "KC" for its location in the nitrocellulose colony hybridization assay.[7]This designation is sometimes erroneously believed to be an acronym and defined as "keratinocytes-derived chemokine". Rat CXCL1 was first reported when NRK-52E (normal rat kidney-52E) cells were stimulated with interleukin-1β (IL-1β) and lipopolysaccharide (LPS) to generate a cytokine that was chemotactic for rat neutrophils, cytokine-induced neutrophil chemoattractant (CINC).[8]In humans, this protein is encoded by thegeneCXCL1[9]and is located on humanchromosome 4among genes for other CXC chemokines.[10]

Structure and expression[edit]

CXCL1 exists as both monomer and dimer and both forms are able to bind chemokine receptorCXCR2.[11]However, CXCL1 chemokine is able to dimerize only at higher (micromolar) concentrations and its concentrations are only nanomolar or picomolar upon normal conditions, which means that the form of WT CXCL1 is more likely monomeric while dimeric CXCL1 is present only during infection or injury. CXCL1 monomer consists of three antiparallelβ-strandsfollowed by C- terminalα-helixand this α-helix together with the first β-strand are involved in forming a dimeric globular structure.[12]

Upon normal conditions, CXCL1 is not expressed constitutively. It's produced by a variety of immune cells such asmacrophages,neutrophilsandepithelial cells,[13][14]orTh17population. Moreover, its expression can be also induced indirectly byIL-1,TNF-αorIL-17produced again by Th17 cells[15]and is triggered mainly by activation ofNF-κBorC/EBPβsignaling pathways predominantly involved ininflammationand leading to production of other inflammatorycytokines.[15]

Function[edit]

CXCL1 has a potentially similar role asinterleukin-8(IL-8/CXCL8). After binding to its receptor CXCR2, CXCL1 activates phosphatidylinositol-4,5-bisphosphate 3-kinase-γ (PI3Kγ)/Akt, MAP kinases such as ERK1/ERK2 or phospholipase-β (PLCβ) signaling pathways. CXCL1 is expressed at higher levels during inflammatory responses thus contributing to the process of inflammation.[16]CXCL1 is also involved in the processes ofwound healingandtumorigenesis.[17][18][19]

Role in cancer[edit]

CXCL1 has a role in angiogenesis and arteriogenesis[20]and thus has been shown to act in the process of tumor progression. The role of CXCL1 was described by several studies in the development of various tumors, such as breast cancer, gastric and colorectal carcinoma or lung cancer.[21][22][23]Also, CXCL1 is secreted by humanmelanomacells, hasmitogenicproperties and is implicated in melanomapathogenesis.[24][25][26]

Role in nervous system and sensitization[edit]

CXCL1 plays a role in spinal cord development by inhibiting the migration of oligodendrocyte precursors.[11]CXCR2 receptor for CXCL1 is expressed in the brain and spinal cord byneuronsand oligodendrocytes and during CNS pathologies such as Alzheimer's disease,multiple sclerosisand brain injury also bymicroglia.An initial study in mice showed evidence that CXCL1 decreased the severity of multiple sclerosis and may offer a neuro-protective function.[27]On the other hand, on the periphery, CXCL1 contributes to the release ofprostaglandinsand thus causes increased sensitivity to pain and drives nociceptive sensitization via recruitment of neutrophils to the tissue. Phosphorylation of ERK1/ERK2 kinases and activation ofNMDA receptorsleads to transcription of genes inducing chronic pain, such asc-Fosorcyclooxygenase-2 (COX-2).[16]

References[edit]

  1. ^abcGRCh38: Ensembl release 89: ENSG00000163739–Ensembl,May 2017
  2. ^abcGRCm38: Ensembl release 89: ENSMUSG00000058427–Ensembl,May 2017
  3. ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^Moser B, Clark-Lewis I, Zwahlen R, Baggiolini M (May 1990)."Neutrophil-activating properties of the melanoma growth-stimulatory activity".The Journal of Experimental Medicine.171(5): 1797–1802.doi:10.1084/jem.171.5.1797.PMC2187876.PMID2185333.
  6. ^Schumacher C, Clark-Lewis I, Baggiolini M, Moser B (November 1992)."High- and low-affinity binding of GRO alpha and neutrophil-activating peptide 2 to interleukin 8 receptors on human neutrophils".Proceedings of the National Academy of Sciences of the United States of America.89(21): 10542–10546.Bibcode:1992PNAS...8910542S.doi:10.1073/pnas.89.21.10542.PMC50375.PMID1438244.
  7. ^Cochran BH, Reffel AC, Stiles CD (July 1983). "Molecular cloning of gene sequences regulated by platelet-derived growth factor".Cell.33(3): 939–947.doi:10.1016/0092-8674(83)90037-5.PMID6872001.S2CID38719612.
  8. ^Watanabe K, Kinoshita S, Nakagawa H (June 1989). "Purification and characterization of cytokine-induced neutrophil chemoattractant produced by epithelioid cell line of normal rat kidney (NRK-52E cell)".Biochemical and Biophysical Research Communications.161(3): 1093–1099.doi:10.1016/0006-291X(89)91355-7.PMID2662972.
  9. ^Haskill S, Peace A, Morris J, Sporn SA, Anisowicz A, Lee SW, et al. (October 1990)."Identification of three related human GRO genes encoding cytokine functions".Proceedings of the National Academy of Sciences of the United States of America.87(19): 7732–7736.Bibcode:1990PNAS...87.7732H.doi:10.1073/pnas.87.19.7732.PMC54822.PMID2217207.
  10. ^Richmond A, Balentien E, Thomas HG, Flaggs G, Barton DE, Spiess J, et al. (July 1988)."Molecular characterization and chromosomal mapping of melanoma growth stimulatory activity, a growth factor structurally related to beta-thromboglobulin".The EMBO Journal.7(7): 2025–2033.doi:10.1002/j.1460-2075.1988.tb03042.x.PMC454478.PMID2970963.
  11. ^abTsai HH, Frost E, To V, Robinson S, Ffrench-Constant C, Geertman R, et al. (August 2002)."The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration".Cell.110(3): 373–383.doi:10.1016/S0092-8674(02)00838-3.PMID12176324.S2CID16880392.
  12. ^Ravindran A, Sawant KV, Sarmiento J, Navarro J, Rajarathnam K (April 2013)."Chemokine CXCL1 dimer is a potent agonist for the CXCR2 receptor".The Journal of Biological Chemistry.288(17): 12244–12252.doi:10.1074/jbc.m112.443762.PMC3636908.PMID23479735.
  13. ^Iida N, Grotendorst GR (October 1990)."Cloning and sequencing of a new gro transcript from activated human monocytes: expression in leukocytes and wound tissue".Molecular and Cellular Biology.10(10): 5596–5599.doi:10.1128/mcb.10.10.5596.PMC361282.PMID2078213.
  14. ^Becker S, Quay J, Koren HS, Haskill JS (March 1994). "Constitutive and stimulated MCP-1, GRO alpha, beta, and gamma expression in human airway epithelium and bronchoalveolar macrophages".The American Journal of Physiology.266(3 Pt 1): L278–L286.doi:10.1152/ajplung.1994.266.3.L278.PMID8166297.
  15. ^abMa K, Yang L, Shen R, Kong B, Chen W, Liang J, et al. (March 2018). "Th17 cells regulate the production of CXCL1 in breast cancer".International Immunopharmacology.56:320–329.doi:10.1016/j.intimp.2018.01.026.PMID29438938.S2CID3568978.
  16. ^abSilva RL, Lopes AH, Guimarães RM, Cunha TM (September 2017). "CXCL1/CXCR2 signaling in pathological pain: Role in peripheral and central sensitization".Neurobiology of Disease.105:109–116.doi:10.1016/j.nbd.2017.06.001.PMID28587921.S2CID4916646.
  17. ^Devalaraja RM, Nanney LB, Du J, Qian Q, Yu Y, Devalaraja MN, Richmond A (August 2000)."Delayed wound healing in CXCR2 knockout mice".The Journal of Investigative Dermatology.115(2): 234–244.doi:10.1046/j.1523-1747.2000.00034.x.PMC2664868.PMID10951241.
  18. ^Haghnegahdar H, Du J, Wang D, Strieter RM, Burdick MD, Nanney LB, et al. (January 2000)."The tumorigenic and angiogenic effects of MGSA/GRO proteins in melanoma".Journal of Leukocyte Biology.67(1): 53–62.doi:10.1002/jlb.67.1.53.PMC2669312.PMID10647998.[permanent dead link]
  19. ^Owen JD, Strieter R, Burdick M, Haghnegahdar H, Nanney L, Shattuck-Brandt R, Richmond A (September 1997)."Enhanced tumor-forming capacity for immortalized melanocytes expressing melanoma growth stimulatory activity/growth-regulated cytokine beta and gamma proteins".International Journal of Cancer.73(1): 94–103.doi:10.1002/(SICI)1097-0215(19970926)73:1<94::AID-IJC15>3.0.CO;2-5.PMID9334815.
  20. ^Vries MH, Wagenaar A, Verbruggen SE, Molin DG, Dijkgraaf I, Hackeng TH, Post MJ (April 2015). "CXCL1 promotes arteriogenesis through enhanced monocyte recruitment into the peri-collateral space".Angiogenesis.18(2): 163–171.doi:10.1007/s10456-014-9454-1.PMID25490937.S2CID52835567.
  21. ^Chen X, Jin R, Chen R, Huang Z (2018-02-01)."Complementary action of CXCL1 and CXCL8 in pathogenesis of gastric carcinoma".International Journal of Clinical and Experimental Pathology.11(2): 1036–1045.PMC6958037.PMID31938199.
  22. ^Hsu YL, Chen YJ, Chang WA, Jian SF, Fan HL, Wang JY, Kuo PL (August 2018)."Interaction between Tumor-Associated Dendritic Cells and Colon Cancer Cells Contributes to Tumor Progression via CXCL1".International Journal of Molecular Sciences.19(8): 2427.doi:10.3390/ijms19082427.PMC6121631.PMID30115896.
  23. ^Spaks A (April 2017)."Role of CXC group chemokines in lung cancer development and progression".Journal of Thoracic Disease.9(Suppl 3): S164–S171.doi:10.21037/jtd.2017.03.61.PMC5392545.PMID28446981.
  24. ^Anisowicz A, Bardwell L, Sager R (October 1987)."Constitutive overexpression of a growth-regulated gene in transformed Chinese hamster and human cells".Proceedings of the National Academy of Sciences of the United States of America.84(20): 7188–7192.Bibcode:1987PNAS...84.7188A.doi:10.1073/pnas.84.20.7188.PMC299255.PMID2890161.
  25. ^Richmond A, Thomas HG (February 1988). "Melanoma growth stimulatory activity: isolation from human melanoma tumors and characterization of tissue distribution".Journal of Cellular Biochemistry.36(2): 185–198.doi:10.1002/jcb.240360209.PMID3356754.S2CID10674236.
  26. ^Dhawan P, Richmond A (July 2002)."Role of CXCL1 in tumorigenesis of melanoma".Journal of Leukocyte Biology.72(1): 9–18.doi:10.1189/jlb.72.1.9.PMC2668262.PMID12101257.
  27. ^Omari KM, Lutz SE, Santambrogio L,Lira SA,Raine CS (January 2009)."Neuroprotection and remyelination after autoimmune demyelination in mice that inducibly overexpress CXCL1".The American Journal of Pathology.174(1): 164–176.doi:10.2353/ajpath.2009.080350.PMC2631329.PMID19095949.

External links[edit]

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