Interleukin-8

Details

Name
Interleukin-8
Kind
protein
Synonyms
  • C-X-C motif chemokine 8
  • Chemokine (C-X-C motif) ligand 8
  • Emoctakin
  • GCP-1
  • Granulocyte chemotactic protein 1
  • IL-8
  • IL8
  • MDNCF
  • MONAP
  • Monocyte-derived neutrophil chemotactic factor
  • Monocyte-derived neutrophil-activating peptide
  • NAP-1
  • Neutrophil-activating protein 1
  • Protein 3-10C
  • T-cell chemotactic factor
Gene Name
CXCL8
UniProtKB Entry
P10145Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0001913|Interleukin-8
MTSKLAVALLAAFLISAALCEGAVLPRSAKELRCQCIKTYSKPFHPKFIKELRVIESGPH
CANTEIIVKLSDGRELCLDPKENWVQRVVEKFLKRAENS
Number of residues
99
Molecular Weight
11097.98
Theoretical pI
9.09
GO Classification
Functions
chemokine activity / interleukin-8 receptor binding
Processes
angiogenesis / calcium-mediated signaling / cellular response to fibroblast growth factor stimulus / cellular response to interleukin-1 / cellular response to lipopolysaccharide / cellular response to tumor necrosis factor / chemokine-mediated signaling pathway / chemotaxis / embryonic digestive tract development / induction of positive chemotaxis / inflammatory response / intracellular signal transduction / neutrophil activation / neutrophil chemotaxis / positive regulation of angiogenesis / positive regulation of neutrophil chemotaxis / receptor internalization / regulation of cell adhesion / regulation of single stranded viral RNA replication via double stranded DNA intermediate / response to endoplasmic reticulum stress / response to molecule of bacterial origin / signal transduction
Components
extracellular region / extracellular space
General Function
Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection (PubMed:18692776, PubMed:7636208). Also plays an important role in neutrophil activation (PubMed:2145175, PubMed:9623510). Released in response to an inflammatory stimulus, exerts its effect by binding to the G-protein-coupled receptors CXCR1 and CXCR2, primarily found in neutrophils, monocytes and endothelial cells (PubMed:1840701, PubMed:1891716). G-protein heterotrimer (alpha, beta, gamma subunits) constitutively binds to CXCR1/CXCR2 receptor and activation by IL8 leads to beta and gamma subunits release from Galpha (GNAI2 in neutrophils) and activation of several downstream signaling pathways including PI3K and MAPK pathways (PubMed:11971003, PubMed:8662698)
Specific Function
chemokine activity
Pfam Domain Function
Signal Regions
1-20
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0010675|Interleukin-8 (CXCL8)
ATGACTTCCAAGCTGGCCGTGGCTCTCTTGGCAGCCTTCCTGATTTCTGCAGCTCTGTGT
GAAGGTGCAGTTTTGCCAAGGAGTGCTAAAGAACTTAGATGTCAGTGCATAAAGACATAC
TCCAAACCTTTCCACCCCAAATTTATCAAAGAACTGAGAGTGATTGAGAGTGGACCACAC
TGCGCCAACACAGAAATTATTGTAAAGCTTTCTGATGGAAGAGAGCTCTGTCTGGACCCC
AAGGAAAACTGGGTGCAGAGGGTTGTGGAGAAGTTTTTGAAGAGGGCTGAGAATTCATAA
Chromosome Location
4
Locus
4q13.3
External Identifiers
ResourceLink
UniProtKB IDP10145
UniProtKB Entry NameIL8_HUMAN
GenBank Protein ID34519
GenBank Gene IDY00787
GeneCard IDCXCL8
GenAtlas IDIL8
HGNC IDHGNC:6025
PDB ID(s)1ICW, 1IKL, 1IKM, 1IL8, 1ILP, 1ILQ, 1QE6, 1ROD, 2IL8, 3IL8, 4XDX, 5D14, 5WDZ, 6LFM, 6LFO, 6N2U, 6WZM, 6XMN, 8IC0
KEGG IDhsa:3576
NCBI Gene ID3576
General References
  1. Schmid J, Weissmann C: Induction of mRNA for a serine protease and a beta-thromboglobulin-like protein in mitogen-stimulated human leukocytes. J Immunol. 1987 Jul 1;139(1):250-6. [Article]
  2. Matsushima K, Morishita K, Yoshimura T, Lavu S, Kobayashi Y, Lew W, Appella E, Kung HF, Leonard EJ, Oppenheim JJ: Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumor necrosis factor. J Exp Med. 1988 Jun 1;167(6):1883-93. [Article]
  3. Mukaida N, Shiroo M, Matsushima K: Genomic structure of the human monocyte-derived neutrophil chemotactic factor IL-8. J Immunol. 1989 Aug 15;143(4):1366-71. [Article]
  4. Kowalski J, Denhardt DT: Regulation of the mRNA for monocyte-derived neutrophil-activating peptide in differentiating HL60 promyelocytes. Mol Cell Biol. 1989 May;9(5):1946-57. [Article]
  5. Hotta K, Hayashi K, Ishikawa J, Tagawa M, Hashimoto K, Mizuno S, Suzuki K: Coding region structure of interleukin-8 gene of human lung giant cell carcinoma LU65C cells that produce LUCT/interleukin-8: homogeneity in interleukin-8 genes. Immunol Lett. 1990 Jun;24(3):165-9. [Article]
  6. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  8. Van Damme J, Van Beeumen J, Conings R, Decock B, Billiau A: Purification of granulocyte chemotactic peptide/interleukin-8 reveals N-terminal sequence heterogeneity similar to that of beta-thromboglobulin. Eur J Biochem. 1989 May 1;181(2):337-44. [Article]
  9. Van Damme J, Rampart M, Conings R, Decock B, Van Osselaer N, Willems J, Billiau A: The neutrophil-activating proteins interleukin 8 and beta-thromboglobulin: in vitro and in vivo comparison of NH2-terminally processed forms. Eur J Immunol. 1990 Sep;20(9):2113-8. [Article]
  10. Yoshimura T, Robinson EA, Appella E, Matsushima K, Showalter SD, Skeel A, Leonard EJ: Three forms of monocyte-derived neutrophil chemotactic factor (MDNCF) distinguished by different lengths of the amino-terminal sequence. Mol Immunol. 1989 Jan;26(1):87-93. [Article]
  11. Suzuki K, Miyasaka H, Ota H, Yamakawa Y, Tagawa M, Kuramoto A, Mizuno S: Purification and partial primary sequence of a chemotactic protein for polymorphonuclear leukocytes derived from human lung giant cell carcinoma LU65C cells. J Exp Med. 1989 Jun 1;169(6):1895-901. [Article]
  12. Schroder JM: Biochemical and biological characterization of NAP-1/IL-8-related cytokines in lesional psoriatic scale. Adv Exp Med Biol. 1991;305:97-107. [Article]
  13. Golds EE, Mason P, Nyirkos P: Inflammatory cytokines induce synthesis and secretion of gro protein and a neutrophil chemotactic factor but not beta 2-microglobulin in human synovial cells and fibroblasts. Biochem J. 1989 Apr 15;259(2):585-8. [Article]
  14. Suzuki K, Yamakawa Y, Matsuo Y, Kamiya T, Minowada J, Mizuno S: Isolation and amino acid sequence of a chemotactic protein, LECT/interleukin 8, from a human myeloid leukemia cell line, ML-1. Immunol Lett. 1993 Apr;36(1):71-81. [Article]
  15. Gregory H, Young J, Schroder JM, Mrowietz U, Christophers E: Structure determination of a human lymphocyte derived neutrophil activating peptide (LYNAP). Biochem Biophys Res Commun. 1988 Mar 15;151(2):883-90. [Article]
  16. Yoshimura T, Matsushima K, Tanaka S, Robinson EA, Appella E, Oppenheim JJ, Leonard EJ: Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9233-7. [Article]
  17. Walz A, Peveri P, Aschauer H, Baggiolini M: Purification and amino acid sequencing of NAF, a novel neutrophil-activating factor produced by monocytes. Biochem Biophys Res Commun. 1987 Dec 16;149(2):755-61. [Article]
  18. Hebert CA, Luscinskas FW, Kiely JM, Luis EA, Darbonne WC, Bennett GL, Liu CC, Obin MS, Gimbrone MA Jr, Baker JB: Endothelial and leukocyte forms of IL-8. Conversion by thrombin and interactions with neutrophils. J Immunol. 1990 Nov 1;145(9):3033-40. [Article]
  19. Clark-Lewis I, Moser B, Walz A, Baggiolini M, Scott GJ, Aebersold R: Chemical synthesis, purification, and characterization of two inflammatory proteins, neutrophil activating peptide 1 (interleukin-8) and neutrophil activating peptide. Biochemistry. 1991 Mar 26;30(12):3128-35. [Article]
  20. Van den Steen PE, Proost P, Wuyts A, Van Damme J, Opdenakker G: Neutrophil gelatinase B potentiates interleukin-8 tenfold by aminoterminal processing, whereas it degrades CTAP-III, PF-4, and GRO-alpha and leaves RANTES and MCP-2 intact. Blood. 2000 Oct 15;96(8):2673-81. [Article]
  21. Schutyser E, Struyf S, Proost P, Opdenakker G, Laureys G, Verhasselt B, Peperstraete L, Van de Putte I, Saccani A, Allavena P, Mantovani A, Van Damme J: Identification of biologically active chemokine isoforms from ascitic fluid and elevated levels of CCL18/pulmonary and activation-regulated chemokine in ovarian carcinoma. J Biol Chem. 2002 Jul 5;277(27):24584-93. Epub 2002 Apr 26. [Article]
  22. Baggiolini M, Clark-Lewis I: Interleukin-8, a chemotactic and inflammatory cytokine. FEBS Lett. 1992 Jul 27;307(1):97-101. [Article]
  23. Struyf S, Proost P, Van Damme J: Regulation of the immune response by the interaction of chemokines and proteases. Adv Immunol. 2003;81:1-44. [Article]
  24. Proost P, Loos T, Mortier A, Schutyser E, Gouwy M, Noppen S, Dillen C, Ronsse I, Conings R, Struyf S, Opdenakker G, Maudgal PC, Van Damme J: Citrullination of CXCL8 by peptidylarginine deiminase alters receptor usage, prevents proteolysis, and dampens tissue inflammation. J Exp Med. 2008 Sep 1;205(9):2085-97. doi: 10.1084/jem.20080305. Epub 2008 Aug 18. [Article]
  25. Loos T, Opdenakker G, Van Damme J, Proost P: Citrullination of CXCL8 increases this chemokine's ability to mobilize neutrophils into the blood circulation. Haematologica. 2009 Oct;94(10):1346-53. doi: 10.3324/haematol.2009.006973. Epub 2009 Jul 16. [Article]
  26. Park SH, Choi HJ, Yang H, Do KH, Kim J, Lee DW, Moon Y: Endoplasmic reticulum stress-activated C/EBP homologous protein enhances nuclear factor-kappaB signals via repression of peroxisome proliferator-activated receptor gamma. J Biol Chem. 2010 Nov 12;285(46):35330-9. doi: 10.1074/jbc.M110.136259. Epub 2010 Sep 9. [Article]
  27. Clore GM, Appella E, Yamada M, Matsushima K, Gronenborn AM: Determination of the secondary structure of interleukin-8 by nuclear magnetic resonance spectroscopy. J Biol Chem. 1989 Nov 15;264(32):18907-11. [Article]
  28. Clore GM, Appella E, Yamada M, Matsushima K, Gronenborn AM: Three-dimensional structure of interleukin 8 in solution. Biochemistry. 1990 Feb 20;29(7):1689-96. [Article]
  29. Sticht H, Auer M, Schmitt B, Besemer J, Horcher M, Kirsch T, Lindley IJ, Rosch P: Structure and activity of a chimeric interleukin-8-melanoma-growth-stimulatory-activity protein. Eur J Biochem. 1996 Jan 15;235(1-2):26-35. [Article]
  30. Skelton NJ, Quan C, Reilly D, Lowman H: Structure of a CXC chemokine-receptor fragment in complex with interleukin-8. Structure. 1999 Feb 15;7(2):157-68. [Article]
  31. Baldwin ET, Franklin KA, Appella E, Yamada M, Matsushima K, Wlodawer A, Weber IT: Crystallization of human interleukin-8. A protein chemotactic for neutrophils and T-lymphocytes. J Biol Chem. 1990 Apr 25;265(12):6851-3. [Article]
  32. Clore GM, Gronenborn AM: Comparison of the solution nuclear magnetic resonance and crystal structures of interleukin-8. Possible implications for the mechanism of receptor binding. J Mol Biol. 1991 Feb 20;217(4):611-20. [Article]
  33. Baldwin ET, Weber IT, St Charles R, Xuan JC, Appella E, Yamada M, Matsushima K, Edwards BF, Clore GM, Gronenborn AM, et al.: Crystal structure of interleukin 8: symbiosis of NMR and crystallography. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):502-6. [Article]
  34. Gerber N, Lowman H, Artis DR, Eigenbrot C: Receptor-binding conformation of the "ELR" motif of IL-8: X-ray structure of the L5C/H33C variant at 2.35 A resolution. Proteins. 2000 Mar 1;38(4):361-7. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
ABT-510investigationalunknowntargetDetails
MDX-018investigationalunknowntargetDetails
RivaniclineinvestigationalunknowntargetantagonistDetails
Human Interleukin 8investigationalyestargetantibodyDetails
Oleandrinexperimental, investigationalunknowntargetinhibitorDetails
IbuprofenapprovedyestargetinhibitorDetails