CXCL5
2MGS
CXCL5（C-X-C motif chemokine ligand 5）またはENA78（epithelial neutrophil-activating protein 78）は、ヒトではCXCL5遺伝子によってコードされているタンパク質である[5][6]。
機能
→「組織リモデリング」も参照
CXCL5遺伝子にコードされるCXCL5タンパク質は、CXCケモカインファミリーに属するサイトカインである。CXCL5は炎症性サイトカインIL-1もしくはTNF-αによって細胞が刺激された後に産生される[7]。CXCL5の発現は好酸球でも観察され、IFN-γによって阻害される[8]。このケモカインは、血管新生促進能を有する好中球の走化性を刺激する。こうした作用は細胞表面のケモカイン受容体CXCR2との相互作用を介して発揮される[8]。CXCL5遺伝子は4つのエクソンから構成され、ヒトの4番染色体上のCXCケモカイン遺伝子クラスター内に位置している[7][9]。CXCL5は結合組織のリモデリングへの関与が示唆されており[8]、また好中球の恒常性を調節することも記載されている[10]。
臨床的意義
CXCL5は一部の患者で日焼けによる痛みの感受性の低下に関与していることが報告されており、関節炎や膀胱炎など他の炎症性疾患における痛みを理解するために有用な標的となる可能性がある[11][12]。CXCL5は、主に急性炎症応答において、好中球に対する走化性と活性化機能が良く知られている。アテローム性動脈硬化（慢性炎症性疾患）においてもCXCL5の発現は上昇しているが、好中球の浸潤とは関連していない。CXCL5はマクロファージの泡沫細胞形成を直接的に制御することで、アテローム動脈硬化に対する保護効果をもたらしている[13]。
出典
- ^ a b c GRCh38: Ensembl release 89: ENSG00000163735 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029371 - Ensembl, May 2017
- ^ Human PubMed Reference:
- ^ Mouse PubMed Reference:
- ^ Chang MS, McNinch J, Basu R, Simonet S (Nov 1994). “Cloning and characterization of the human neutrophil-activating peptide (ENA-78) gene”. J Biol Chem 269 (41): 25277–82. doi:10.1016/S0021-9258(18)47243-2. PMID 7929219.
- ^ “Entrez Gene: CXCL5 chemokine (C-X-C motif) ligand 5”. 2025年10月13日閲覧。
- ^ a b Chang MS, McNinch J, Basu R, Simonet S (1994). “Cloning and characterization of the human neutrophil-activating peptide (ENA-78) gene”. J. Biol. Chem. 269 (41): 25277–82. doi:10.1016/S0021-9258(18)47243-2. PMID 7929219.
- ^ a b c Persson T, Monsef N, Andersson P, Bjartell A, Malm J, Calafat J, Egesten A (2003). “Expression of the neutrophil-activating CXC chemokine ENA-78/CXCL5 by human eosinophils”. Clin. Exp. Allergy 33 (4): 531–7. doi:10.1046/j.1365-2222.2003.01609.x. PMID 12680872.
- ^ 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.
- ^ Mei J, Liu Y, Dai N, Hoffmann C, Hudock KM, Zhang P, Guttentag SH, Kolls JK, Oliver PM, Bushman FD, Worthen GS (2012). “Cxcr2 and Cxcl5 regulate the IL-17/G-CSF axis and neutrophil homeostasis in mice”. Journal of Clinical Investigation 122 (3): 974–986. doi:10.1172/JCI60588. PMC 3287232. PMID 22326959.
- ^ Dawes, John M.; Calvo, Margarita; Perkins, James R.; Paterson, Kathryn J.; Kiesewetter, Hannes; Hobbs, Carl; Kaan, Timothy K. Y.; Orengo, Christine et al. (2011-07-06). “CXCL5 mediates UVB irradiation-induced pain”. Science Translational Medicine 3 (90): 90ra60. doi:10.1126/scitranslmed.3002193. ISSN 1946-6242. PMC 3232447. PMID 21734176.
- ^ “Sunburn pain discovery could lead to better arthritis treatments” (英語). www.fiercebiotechresearch.com. 2011年7月13日時点のオリジナルよりアーカイブ。2025年10月13日閲覧。
- ^ Rousselle A, Qadri F, Leukel L, Yilmaz R, Fontaine JF, Sihn G, Bader M, Ahluwalia A, Duchene J (2013). “CXCL5 limits macrophage foam cell formation in atherosclerosis.”. Journal of Clinical Investigation 123 (3): 1343–7. doi:10.1172/JCI66580. PMC 3582141. PMID 23376791.
関連文献
- Duchene J, Lecomte F, Ahmed S, Cayla C, Pesquero J, Bader M, Perretti M, Ahluwalia A (2007). “A novel inflammatory pathway involved in leukocyte recruitment: role for the kinin B1 receptor and the chemokine CXCL5”. J. Immunol. 179 (7): 4849–56. doi:10.4049/jimmunol.179.7.4849. PMC 3696729. PMID 17878384.
- Walz A, Schmutz P, Mueller C, Schnyder-Candrian S (1997). “Regulation and function of the CXC chemokine ENA-78 in monocytes and its role in disease”. J. Leukoc. Biol. 62 (5): 604–11. doi:10.1002/jlb.62.5.604. PMID 9365115.
- Struyf S, Proost P, Van Damme J (2004). Regulation of the Immune Response by the Interaction of Chemokines and Proteases. Advances in Immunology. 81. pp. 1–44. doi:10.1016/S0065-2776(03)81001-5. ISBN 978-0-12-022481-4. PMID 14711052
- Walz A, Burgener R, Car B (1992). “Structure and neutrophil-activating properties of a novel inflammatory peptide (ENA-78) with homology to interleukin 8”. J. Exp. Med. 174 (6): 1355–62. doi:10.1084/jem.174.6.1355. PMC 2119025. PMID 1744577.
- Power CA, Furness RB, Brawand C, Wells TN (1995). “Cloning of a full-length cDNA encoding the neutrophil-activating peptide ENA-78 from human platelets”. Gene 151 (1–2): 333–4. doi:10.1016/0378-1119(94)90682-3. PMID 7828901.
- Corbett MS, Schmitt I, Riess O, Walz A (1995). “Characterization of the gene for human neutrophil-activating peptide 78 (ENA-78)”. Biochem. Biophys. Res. Commun. 205 (1): 612–7. doi:10.1006/bbrc.1994.2709. PMID 7999089.
- Koch AE, Kunkel SL, Harlow LA (1994). “Epithelial neutrophil activating peptide-78: a novel chemotactic cytokine for neutrophils in arthritis”. J. Clin. Invest. 94 (3): 1012–8. doi:10.1172/JCI117414. PMC 295150. PMID 8083342.
- Power CA, Clemetson JM, Clemetson KJ, Wells TN (1996). “Chemokine and chemokine receptor mRNA expression in human platelets”. Cytokine 7 (6): 479–82. doi:10.1006/cyto.1995.0065. PMID 8580362.
- Ahuja SK, Murphy PM (1996). “The CXC chemokines growth-regulated oncogene (GRO) alpha, GRObeta, GROgamma, neutrophil-activating peptide-2, and epithelial cell-derived neutrophil-activating peptide-78 are potent agonists for the type B, but not the type A, human interleukin-8 receptor”. J. Biol. Chem. 271 (34): 20545–50. doi:10.1074/jbc.271.34.20545. PMID 8702798.
- Keates S, Keates AC, Mizoguchi E (1997). “Enterocytes are the primary source of the chemokine ENA-78 in normal colon and ulcerative colitis”. Am. J. Physiol. 273 (1 Pt 1): G75–82. doi:10.1152/ajpgi.1997.273.1.G75. PMID 9252512.
- Wuyts A, Proost P, Lenaerts JP (1998). “Differential usage of the CXC chemokine receptors 1 and 2 by interleukin-8, granulocyte chemotactic protein-2 and epithelial-cell-derived neutrophil attractant-78”. Eur. J. Biochem. 255 (1): 67–73. doi:10.1046/j.1432-1327.1998.2550067.x. PMID 9692902.
- Wyrick PB, Knight ST, Paul TR (1999). “Persistent chlamydial envelope antigens in antibiotic-exposed infected cells trigger neutrophil chemotaxis”. J. Infect. Dis. 179 (4): 954–66. doi:10.1086/314676. PMID 10068592.
- Wuyts A, Govaerts C, Struyf S (1999). “Isolation of the CXC chemokines ENA-78, GRO alpha and GRO gamma from tumor cells and leukocytes reveals NH2-terminal heterogeneity. Functional comparison of different natural isoforms”. Eur. J. Biochem. 260 (2): 421–9. doi:10.1046/j.1432-1327.1999.00166.x. PMID 10095777.
- Hogaboam CM, Bone-Larson CL, Steinhauser ML (1999). “Novel CXCR2-dependent liver regenerative qualities of ELR-containing CXC chemokines”. FASEB J. 13 (12): 1565–74. doi:10.1096/fasebj.13.12.1565. hdl:2027.42/154508. PMID 10463948.
- Luu NT, Rainger GE, Nash GB (2000). “Differential ability of exogenous chemotactic agents to disrupt transendothelial migration of flowing neutrophils”. J. Immunol. 164 (11): 5961–9. doi:10.4049/jimmunol.164.11.5961. PMID 10820279.
- Crane IJ, Wallace CA, McKillop-Smith S, Forrester JV (2000). “Control of chemokine production at the blood–retina barrier”. Immunology 101 (3): 426–33. doi:10.1046/j.0019-2805.2000.01105.x. PMC 2327097. PMID 11106948.
- Zhang C, Thornton MA, Kowalska MA (2001). “Localization of distal regulatory domains in the megakaryocyte-specific platelet basic protein/platelet factor 4 gene locus”. Blood 98 (3): 610–7. doi:10.1182/blood.V98.3.610. PMID 11468158.
- Chandrasekar B, Melby PC, Sarau HM (2003). “Chemokine-cytokine cross-talk. The ELR+ CXC chemokine LIX (CXCL5) amplifies a proinflammatory cytokine response via a phosphatidylinositol 3-kinase-NF-kappa B pathway”. J. Biol. Chem. 278 (7): 4675–86. doi:10.1074/jbc.M207006200. PMID 12468547.
- Strausberg RL, Feingold EA, Grouse LH (2003). “Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences”. Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
外部リンク
- Human CXCL5 genome location and CXCL5 gene details page in the UCSC Genome Browser.
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