Interleukin 8

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Chemokine (C-X-C motif) ligand 8
IL8 Solution Structure.rsh.png
PDB rendering based on 1IL8.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CXCL8 ; GCP-1; GCP1; IL8; LECT; LUCT; LYNAP; MDNCF; MONAP; NAF; NAP-1; NAP1
External IDs OMIM146930 HomoloGene47937 ChEMBL: 2157 GeneCards: CXCL8 Gene
RNA expression pattern
PBB GE IL8 211506 s at.png
PBB GE IL8 202859 x at.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3576 n/a
Ensembl ENSG00000169429 n/a
UniProt P10145 n/a
RefSeq (mRNA) NM_000584 n/a
RefSeq (protein) NP_000575 n/a
Location (UCSC) Chr 4:
74.61 – 74.61 Mb
n/a
PubMed search [1] 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). Toll-like receptors are the receptors of the innate immune system. These receptors recognize antigen patterns (like LPS in gram negative bacteria). 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[edit]

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[edit]

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[edit]

Interleukin-8 is often associated with inflammation. As an example, it has been cited as a proinflammatory mediator in gingivitis[8] and psoriasis.[2]. 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.[9] IL-8 was shown to be associated with obesity.[10]

If a pregnant mother has high levels of interleukin-8, there is an increased risk of schizophrenia in her offspring.[11] High levels of Interleukin 8 have been shown to reduce the likelihood of positive responses to antipsychotic medication in schizophrenia.[12]

Nomenclature[edit]

IL-8 was renamed CXCL8 by the Chemokine Nomenclature Subcommittee of the International Union of Immunological Societies,.[13] Its approved HUGO gene symbol is CXCL8.

Regulation of Expression[edit]

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.[14] 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.[15] NF-κB regulation represents a novel anti-IL-8 therapy for use in inflammatory diseases such as cystic fibrosis.

See also[edit]


References[edit]

  1. ^ Hedges JC, Singer CA, Gerthoffer WT (July 2000). "Mitogen-activated protein kinases regulate cytokine gene expression in human airway myocytes". Am. J. Respir. Cell Mol. Biol. 23 (1): 86–94. doi:10.1165/ajrcmb.23.1.4014. PMID 10873157. 
  2. ^ Wolff B, Burns AR, Middleton J, Rot A (November 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. doi:10.1084/jem.188.9.1757. PMC 2212526. PMID 9802987. 
  3. ^ Utgaard JO, Jahnsen FL, Bakka A, Brandtzaeg P, Haraldsen G (November 1998). "Rapid secretion of prestored interleukin 8 from Weibel-Palade bodies of microvascular endothelial cells". J. Exp. Med. 188 (9): 1751–6. doi:10.1084/jem.188.9.1751. PMC 2212514. PMID 9802986. 
  4. ^ a b Modi WS, Dean M, Seuanez HN, Mukaida N, Matsushima K, O'Brien SJ (January 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. doi:10.1007/BF00208938. PMID 1967588. 
  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 (July 1998). "Chemotaxis and chemotactic selection induced with cytokines (IL-8, RANTES and TNF-alpha) in the unicellular Tetrahymena pyriformis". Cytokine 10 (7): 481–6. doi:10.1006/cyto.1997.0328. PMID 9702410. 
  8. ^ 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.
  9. ^ Vlahopoulos S, Boldogh I, Casola A, Brasier AR (September 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. PMID 10477716. 
  10. ^ Sharabiani, M.T.; Vermeulen R, Scoccianti C, Hosnijeh FS, Minelli L, Sacerdote C, Palli D, Krogh V, Tumino R, Chiodini P, Panico S, Vineis P. (May 2011). "Immunologic profile of excessive body weight". Biomarkers 16 (3): 243–51. doi:10.3109/1354750X.2010.547948. PMID 21506696. 
  11. ^ Brown AS, Hooton J, Schaefer CA, Zhang H, Petkova E, Babulas V, Perrin M, Gorman JM, Susser ES (May 2004). "Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring". Am J Psychiatry 161 (5): 889–95. doi:10.1176/appi.ajp.161.5.889. PMID 15121655. 
  12. ^ Zhang XY, Zhou DF, Cao LY, Zhang PY, Wu GY, Shen YC (July 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. doi:10.4088/JCP.v65n0710. PMID 15291683. 
  13. ^ 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 (October 2002). "Chemokine/chemokine receptor nomenclature". J. Interferon Cytokine Res. 22 (10): 1067–8. doi:10.1089/107999002760624305. PMID 12433287. 
  14. ^ Bhaumik D, Scott GK, Schokrpur S, Patil CK, Orjalo AV, Rodier F, Lithgow GJ, Campisi J (April 2009). "MicroRNAs miR-146a/b negatively modulate the senescence-associated inflammatory mediators IL-6 and IL-8". Aging (Albany NY) 1 (4): 402–11. PMC 2818025. PMID 20148189. 
  15. ^ Rottner, Mathilde; Freyssinet, Martinez (2009). "Mechanisms of the noxious inflammatory cycle in cystic fibrosis". Respiratory Research 10: 1–11. doi:10.1186/1465-9921-10-23.  |first3= missing |last3= in Authors list (help)

Further reading[edit]

  • Baggiolini M, Clark-Lewis I (1992). "Interleukin-8, a chemotactic and inflammatory cytokine". FEBS Lett. 307 (1): 97–101. doi:10.1016/0014-5793(92)80909-Z. PMID 1639201. 
  • Wahl SM, Greenwell-Wild T, Hale-Donze H et al. (2000). "Permissive factors for HIV-1 infection of macrophages". J. Leukoc. Biol. 68 (3): 303–10. PMID 10985244. 
  • Starckx S, Van den Steen PE, Wuyts A et al. (2003). "Neutrophil gelatinase B and chemokines in leukocytosis and stem cell mobilization". Leuk. Lymphoma 43 (2): 233–41. doi:10.1080/10428190290005982. PMID 11999552. 
  • Smirnova MG, Kiselev SL, Gnuchev NV et al. (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. PMID 12101072. 
  • Struyf S, Proost P, Van Damme J (2004). "Regulation of the immune response by the interaction of chemokines and proteases". Adv. Immunol. Advances in Immunology 81: 1–44. doi:10.1016/S0065-2776(03)81001-5. ISBN 978-0-12-022481-4. PMID 14711052. 
  • Chakravorty M, Ghosh A, Choudhury A et al. (2004). "Ethnic differences in allele distribution for the IL8 and IL1B genes in populations from eastern India". Hum. Biol. 76 (1): 153–9. doi:10.1353/hub.2004.0016. PMID 15222686. 
  • Yuan A, Chen JJ, Yao PL, Yang PC (2006). "The role of interleukin-8 in cancer cells and microenvironment interaction". Front. Biosci. 10: 853–65. doi:10.2741/1579. PMID 15569594. 
  • Copeland KF (2006). "Modulation of HIV-1 transcription by cytokines and chemokines". Mini reviews in medicinal chemistry 5 (12): 1093–101. doi:10.2174/138955705774933383. PMID 16375755.