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Interleukin 8

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Title: Interleukin 8  
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Subject: Interleukin, Interleukin 8 receptor, alpha, Outline of immunology, Interleukin 8 receptor, beta, IL-8
Collection: Cytokines
Publisher: World Heritage Encyclopedia

Interleukin 8

Chemokine (C-X-C motif) ligand 8
PDB rendering based on 1IL8.
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs ChEMBL: GeneCards:
RNA expression pattern
Species Human Mouse
Entrez n/a
Ensembl n/a
UniProt n/a
RefSeq (mRNA) n/a
RefSeq (protein) n/a
Location (UCSC) n/a
PubMed search n/a

Interleukin 8 (IL-8) or CXCL8 is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells[1] and endothelial cells. Endothelial cells store IL-8 in their storage vesicles, the Weibel-Palade bodies.[2][3] In humans, the interleukin-8 protein is encoded by the IL8 gene.[4] IL-8 is initially produced as a precursor peptide of 99 amino acids long which then undergoes cleavage to create several active IL-8 isoforms.[5] In culture, a 72 amino acid peptide is the major form secreted by macrophages.[5]

There are many receptors on the surface membrane capable of binding IL-8; the most frequently studied types are the G protein-coupled serpentine receptors CXCR1 and CXCR2. Expression and affinity for IL-8 differs between the two receptors (CXCR1 > CXCR2). Through a chain of biochemical reactions, IL-8 is secreted and is an important mediator of the immune reaction in the innate immune system response.


  • Function 1
  • Target cells 2
  • Clinical significance 3
  • Nomenclature 4
  • Regulation of Expression 5
  • See also 6
  • References 7
  • Further reading 8


IL-8, also known as neutrophil chemotactic factor, has two primary functions. It induces chemotaxis in target cells, primarily neutrophils but also other granulocytes, causing them to migrate toward the site of infection. IL-8 also induces phagocytosis once they have arrived. IL-8 is also known to be a potent promoter of angiogenesis. In target cells, IL-8 induces a series of physiological responses required for migration and phagocytosis, such as increases in intracellular Ca2+, exocytosis (e.g. histamine release), and the respiratory burst.

IL-8 can be secreted by any cells with toll-like receptors that are involved in the innate immune response. Usually, it is the macrophages that see an antigen first, and thus are the first cells to release IL-8 to recruit other cells. Both monomer and homodimer forms of IL-8 have been reported to be potent inducers of the chemokine receptors CXCR1 and CXCR2. The homodimer is more potent, but methylation of Leu25 can block the activity of homodimers.

IL-8 is believed to play a role in the pathogenesis of bronchiolitis, a common respiratory tract disease caused by viral infection.{fact}

IL-8 is a member of the CXC chemokine family. The genes encoding this and the other ten members of the CXC chemokine family form a cluster in a region mapped to chromosome 4q.[4][6]

Target cells

While neutrophil granulocytes are the primary target cells of IL-8, there are a relatively wide range of cells (endothelial cells, macrophages, mast cells, and keratinocytes) that respond to this chemokine. The chemoattractant activity of IL-8 in similar concentrations to vertebrates was proven in Tetrahymena pyriformis, which suggests a phylogenetically well-conserved structure and function for this chemokine.[7]

Clinical significance

Interleukin-8 is a key mediator associated with inflammation where it plays a key role in neutrophil recruitment and neutrophil degranulation.[8] As an example, it has been cited as a proinflammatory mediator in gingivitis[9] and psoriasis.[4].

Interleukin-8 secretion is increased by oxidant stress, which thereby cause the recruitment of inflammatory cells and induces a further increase in oxidant stress mediators, making it a key parameter in localized inflammation.[10] IL-8 was shown to be associated with obesity.[11]

IL-8 has also been implied to have a role in colorectal cancer by acting as an autocrine growth factor for colon carcinoma cell lines[12] or the promotion of division and possible migration by cleaving metalloproteinase molecules.[13]

If a pregnant mother has high levels of interleukin-8, there is an increased risk of schizophrenia in her offspring.[14] High levels of Interleukin 8 have been shown to reduce the likelihood of positive responses to antipsychotic medication in schizophrenia.[15]

IL-8 has also been implicated in the pathology of cystic fibrosis. Through its action as a signalling molecule IL-8 is capable of recruiting and guiding neutrophils to the lung epithelium. Overstimulation and dysfunction of these recruited neutrophils within the airways results in release of a number of pro-inflammatory molecules and proteases resulting in further damage of lung tissue.[16]


IL-8 was renamed CXCL8 by the Chemokine Nomenclature Subcommittee of the HUGO gene symbol is CXCL8.

Regulation of Expression

The expression of IL-8 is negatively regulated by a number of mechanisms. MiRNA-146a/b-5p indirectly represses IL-8 expression by silencing the expression of IRAK1.[18] Additionally, the 3'UTR of IL-8 contains a A/U-rich element that makes it extremely unstable under certain conditions. IL-8 expression is also regulated by the transcription factor NF-κB.[19] NF-κB regulation represents a novel anti-IL-8 therapy for use in inflammatory diseases such as cystic fibrosis.

See also


  1. ^ Hedges JC, Singer CA, Gerthoffer WT (2000). "Mitogen-activated protein kinases regulate cytokine gene expression in human airway myocytes". Am. J. Respir. Cell Mol. Biol. 23 (1): 86–94.  
  2. ^ Wolff B, Burns AR, Middleton J, Rot A (1998). "Endothelial cell "memory" of inflammatory stimulation: human venular endothelial cells store interleukin 8 in Weibel-Palade bodies". J. Exp. Med. 188 (9): 1757–62.  
  3. ^ Utgaard JO, Jahnsen FL, Bakka A, Brandtzaeg P, Haraldsen G (1998). "Rapid secretion of prestored interleukin 8 from Weibel-Palade bodies of microvascular endothelial cells". J. Exp. Med. 188 (9): 1751–6.  
  4. ^ a b Modi WS, Dean M, Seuanez HN, Mukaida N, Matsushima K, O'Brien SJ (1990). "Monocyte-derived neutrophil chemotactic factor (MDNCF/IL-8) resides in a gene cluster along with several other members of the platelet factor 4 gene superfamily". Hum. Genet. 84 (2): 185–7.  
  5. ^ a b Brat DJ, Bellail AC, and Van Meir EG. 2005. The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis. Neuro-oncology. 7(2), pages 122-133
  6. ^ "Entrez Gene: IL8 interleukin 8". 
  7. ^ Köhidai L, Csaba G (1998). "Chemotaxis and chemotactic selection induced with cytokines (IL-8, RANTES and TNF-alpha) in the unicellular Tetrahymena pyriformis". Cytokine 10 (7): 481–6.  
  8. ^ Harada A, Sekido N, Akahoshi T, Wada T, Mukaida N, Matsushima K (Nov 1994). "Essential involvement of interleukin-8 (IL-8) in acute inflammation". Journal of Leukocyte Biology 56 (5): 559–64.  
  9. ^ Haake, SK, Huang, GTJ: Molecular Biology of the host-Microbe Interaction in Periodontal Diseases (Selected Topics). In Newman, Takei, Carranza, editors: Clinical Periodontology, 9th Edition. Philadelphia: W.B.Saunders Co. 2002. page 162.
  10. ^ Vlahopoulos S, Boldogh I, Casola A, Brasier AR (1999). "Nuclear factor-kappaB-dependent induction of interleukin-8 gene expression by tumor necrosis factor alpha: evidence for an antioxidant sensitive activating pathway distinct from nuclear translocation". Blood 94 (6): 1878–89.  
  11. ^ Sharabiani MT, Vermeulen R, Scoccianti C, Hosnijeh FS, Minelli L, Sacerdote C, Palli D, Krogh V, Tumino R, Chiodini P, Panico S, Vineis P (2011). "Immunologic profile of excessive body weight". Biomarkers 16 (3): 243–51.  
  12. ^ Brew R, Erikson JS, West DC, Kinsella AR, Slavin J, Christmas SE (2000). "Interleukin-8 as an autocrine growth factor for human colon carcinoma cells in vitro". Cytokine 12 (1): 78–85.  
  13. ^ Itoh Y, Joh T, Tanida S, Sasaki M, Kataoka H, Itoh K, Oshima T, Ogasawara N, Togawa S, Wada T, Kubota H, Mori Y, Ohara H, Nomura T, Higashiyama S, Itoh M (2005). "IL-8 promotes cell proliferation and migration through metalloproteinase-cleavage proHB-EGF in human colon carcinoma cells". Cytokine 29 (6).  
  14. ^ Brown AS, Hooton J, Schaefer CA, Zhang H, Petkova E, Babulas V, Perrin M, Gorman JM, Susser ES (2004). "Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring". Am J Psychiatry 161 (5): 889–95.  
  15. ^ Zhang XY, Zhou DF, Cao LY, Zhang PY, Wu GY, Shen YC (2004). "Changes in serum interleukin-2, -6, and -8 levels before and during treatment with risperidone and haloperidol: relationship to outcome in schizophrenia". J Clin Psychiatry 65 (7): 940–7.  
  16. ^ Reeves EP, Williamson M, O'Neill SJ, Greally P, McElvaney NG (Jun 2011). "Nebulized hypertonic saline decreases IL-8 in sputum of patients with cystic fibrosis". American Journal of Respiratory and Critical Care Medicine 183 (11): 1517–23.  
  17. ^ Bacon K, Baggiolini M, Broxmeyer H, Horuk R, Lindley I, Mantovani A, Maysushima K, Murphy P, Nomiyama H, Oppenheim J, Rot A, Schall T, Tsang M, Thorpe R, Van Damme J, Wadhwa M, Yoshie O, Zlotnik A, Zoon K (2002). "Chemokine/chemokine receptor nomenclature". J. Interferon Cytokine Res. 22 (10): 1067–8.  
  18. ^ Bhaumik D, Scott GK, Schokrpur S, Patil CK, Orjalo AV, Rodier F, Lithgow GJ, Campisi J (2009). "MicroRNAs miR-146a/b negatively modulate the senescence-associated inflammatory mediators IL-6 and IL-8". Aging (Albany NY) 1 (4): 402–11.  
  19. ^ Rottner M, Freyssinet JM, Martínez MC (2009). "Mechanisms of the noxious inflammatory cycle in cystic fibrosis". Respir. Res. 10 (1): 23.  

Further reading

  • Baggiolini M, Clark-Lewis I (1992). "Interleukin-8, a chemotactic and inflammatory cytokine". FEBS Lett. 307 (1): 97–101.  
  • Wahl SM, Greenwell-Wild T, Hale-Donze H, Moutsopoulos N, Orenstein JM (2000). "Permissive factors for HIV-1 infection of macrophages". J. Leukoc. Biol. 68 (3): 303–10.  
  • Starckx S, Van den Steen PE, Wuyts A, Van Damme J, Opdenakker G (2002). "Neutrophil gelatinase B and chemokines in leukocytosis and stem cell mobilization". Leuk. Lymphoma 43 (2): 233–41.  
  • Smirnova MG, Kiselev SL, Gnuchev NV, Birchall JP, Pearson JP (2003). "Role of the pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6 and interleukin-8 in the pathogenesis of the otitis media with effusion". Eur. Cytokine Netw. 13 (2): 161–72.  
  • Struyf S, Proost P, Van Damme J (2003). "Regulation of the immune response by the interaction of chemokines and proteases". Adv. Immunol. Advances in Immunology 81: 1–44.  
  • Chakravorty M, Ghosh A, Choudhury A, Santra A, Hembrum J, Roychoudhury S (2004). "Ethnic differences in allele distribution for the IL8 and IL1B genes in populations from eastern India". Hum. Biol. 76 (1): 153–9.  
  • Yuan A, Chen JJ, Yao PL, Yang PC (2005). "The role of interleukin-8 in cancer cells and microenvironment interaction". Front. Biosci. 10: 853–65.  
  • Copeland KF (2005). "Modulation of HIV-1 transcription by cytokines and chemokines". Mini Rev Med Chem 5 (12): 1093–101.  
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