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Gene Review

CXCL8  -  chemokine (C-X-C motif) ligand 8

Homo sapiens

Synonyms: 3-10C, AMCF-I, C-X-C motif chemokine 8, Chemokine (C-X-C motif) ligand 8, Emoctakin, ...
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Disease relevance of IL8

  • Additionally, we found that an IL8 promoter polymorphism had a protective effect for lung cancer in female subjects, whereas an IL6 promoter polymorphism was only associated with risk of squamous cell carcinoma [1].
  • Homozygous carriers of the IL8 -251-A allele were at 2.7-fold increased risk of adenoma (95% CI, 1.5-4.9) compared with homozygosity for the common T allele, whereas carriage of at least one IL8 -251-A allele conferred a 1.5 increased odds of disease (95% CI, 1.0-2.4) [2].
  • We show that pepducins derived from either the i1 or i3 intracellular loops of CXCR1 and CXCR2 prevent the IL-8 response of both receptors and reverse the lethal sequelae of sepsis, including disseminated intravascular coagulation and multi-organ failure in mice [3].
  • Here, we demonstrate expression of interleukin (IL)-8, a cytokine with chemotactic and angiogenic properties, and of IL-8-binding receptors in astrocytoma [4].
  • Upregulation of interleukin 8 by oxygen-deprived cells in glioblastoma suggests a role in leukocyte activation, chemotaxis, and angiogenesis [4].
  • IL-8 is a molecular determinant of androgen-independent prostate cancer growth and progression [5].

Psychiatry related information on IL8


High impact information on IL8

  • Interleukin 8, the first chemokine to be characterized, was discovered nearly ten years ago [11].
  • The primary structures of leukocyte receptors for N-formyl peptides, C5a, platelet-activating factor, and 8 of the 18 known human chemokines (interleukin-8 and related molecules) have been deduced from cloned cDNAs [12].
  • EPIs inhibit the growth of epithelial cells but induce them to secrete the neutrophil attractant IL-8, while PEPI blocks neutrophil activation by tumor necrosis factor, preventing release of oxidants and proteases [13].
  • Before treatment, the concentrations of interleukin-8 in the cerebrospinal fluid were inversely related to the duration of neuralgia in all the patients (r=-0.49, P<0.001) [14].
  • In the patients who received methylprednisolone, interleukin-8 concentrations decreased by 50 percent, and this decrease correlated with the duration of neuralgia and with the extent of global pain relief (P<0.001 for both comparisons) [14].

Chemical compound and disease context of IL8


Biological context of IL8


Anatomical context of IL8

  • In addition, IL8-mediated LAK cell migration was inhibited by 8-Br-cADPR and a protein kinase G inhibitor [24].
  • It can be concluded that the platelet factor beta TG, structurally related to the monokine IL8, can also play a role in neutrophil activation during inflammatory reactions [25].
  • Epithelial cells were selectively stained by antibodies to IL6, IL8 and TNF-alpha both in primary cultures and in the normal mammary gland [26].
  • In the presence of a vasodilator substance low doses (2-20 pmol) of IL8 and the shorter forms of beta TG caused granulocyte accumulation and plasma leakage in rabbit skin whereas the longer forms of beta TG again failed to do so [25].
  • By contrast, resting RA and control macrophages produce similar levels of IL8 mRNA [27].

Associations of IL8 with chemical compounds


Physical interactions of IL8

  • The simultaneous treatment with ATRA and TNF-alpha also resulted in changes in the composition of NF-kappaB complexes bound to the IL-8 NF-kappaB site, preventing the formation of two TNF-alpha-inducible binding activities [31].
  • 125I-MGSA binding was specific and could not be displaced by unlabeled IL-8 [32].
  • This confirms the importance of this region in IL-8 in receptor binding and in conferring specificity between CXC and CC chemokines [33].
  • It is an antagonist of 125I-IL-8 binding to CXCR2 with an IC50 = 22 nM [34].
  • Scatchard analysis of 125I-IL-8 binding to erythrocyte membranes and to dodecyl beta-maltoside solubilized CK receptors revealed a single class of high affinity binding sites in both cases with KD values of 9.5 nM +/- 3.6 and 15.4 nM +/- 5.0, respectively [35].
  • We found that IL-8 binds to immobilized VWF under the slightly acidic conditions thought to prevail in the lumen of the late secretory pathway [36].

Enzymatic interactions of IL8


Regulatory relationships of IL8


Other interactions of IL8


Analytical, diagnostic and therapeutic context of IL8


  1. Association of a common polymorphism in the cyclooxygenase 2 gene with risk of non-small cell lung cancer. Campa, D., Zienolddiny, S., Maggini, V., Skaug, V., Haugen, A., Canzian, F. Carcinogenesis (2004) [Pubmed]
  2. Inflammation-related gene polymorphisms and colorectal adenoma. Gunter, M.J., Canzian, F., Landi, S., Chanock, S.J., Sinha, R., Rothman, N. Cancer Epidemiol. Biomarkers Prev. (2006) [Pubmed]
  3. Reversing systemic inflammatory response syndrome with chemokine receptor pepducins. Kaneider, N.C., Agarwal, A., Leger, A.J., Kuliopulos, A. Nat. Med. (2005) [Pubmed]
  4. Upregulation of interleukin 8 by oxygen-deprived cells in glioblastoma suggests a role in leukocyte activation, chemotaxis, and angiogenesis. Desbaillets, I., Diserens, A.C., Tribolet, N., Hamou, M.F., Van Meir, E.G. J. Exp. Med. (1997) [Pubmed]
  5. Interleukin-8 is a molecular determinant of androgen independence and progression in prostate cancer. Araki, S., Omori, Y., Lyn, D., Singh, R.K., Meinbach, D.M., Sandman, Y., Lokeshwar, V.B., Lokeshwar, B.L. Cancer Res. (2007) [Pubmed]
  6. Inhibition of long-term potentiation by interleukin-8: implications for human immunodeficiency virus-1-associated dementia. Xiong, H., Boyle, J., Winkelbauer, M., Gorantla, S., Zheng, J., Ghorpade, A., Persidsky, Y., Carlson, K.A., Gendelman, H.E. J. Neurosci. Res. (2003) [Pubmed]
  7. Elevated interleukin-2, interleukin-6 and interleukin-8 serum levels in neuroleptic-free schizophrenia: association with psychopathology. Zhang, X.Y., Zhou, D.F., Zhang, P.Y., Wu, G.Y., Cao, L.Y., Shen, Y.C. Schizophr. Res. (2002) [Pubmed]
  8. Local and systemic inflammation in patients with chronic obstructive pulmonary disease: soluble tumor necrosis factor receptors are increased in sputum. Vernooy, J.H., Küçükaycan, M., Jacobs, J.A., Chavannes, N.H., Buurman, W.A., Dentener, M.A., Wouters, E.F. Am. J. Respir. Crit. Care Med. (2002) [Pubmed]
  9. Stimulated production of interleukin-8 covaries with psychosocial risk factors for inflammatory disease among middle-aged community volunteers. Marsland, A.L., Sathanoori, R., Muldoon, M.F., Manuck, S.B. Brain Behav. Immun. (2007) [Pubmed]
  10. Regional cerebral blood flow and cytokines in young females with fibromyalgia. Gur, A., Karakoc, M., Erdogan, S., Nas, K., Cevik, R., Sarac, A.J. Clinical and experimental rheumatology. (2002) [Pubmed]
  11. Human chemokines: an update. Baggiolini, M., Dewald, B., Moser, B. Annu. Rev. Immunol. (1997) [Pubmed]
  12. The molecular biology of leukocyte chemoattractant receptors. Murphy, P.M. Annu. Rev. Immunol. (1994) [Pubmed]
  13. Conversion of proepithelin to epithelins: roles of SLPI and elastase in host defense and wound repair. Zhu, J., Nathan, C., Jin, W., Sim, D., Ashcroft, G.S., Wahl, S.M., Lacomis, L., Erdjument-Bromage, H., Tempst, P., Wright, C.D., Ding, A. Cell (2002) [Pubmed]
  14. Intrathecal methylprednisolone for intractable postherpetic neuralgia. Kotani, N., Kushikata, T., Hashimoto, H., Kimura, F., Muraoka, M., Yodono, M., Asai, M., Matsuki, A. N. Engl. J. Med. (2000) [Pubmed]
  15. Net inflammatory capacity of human septic shock plasma evaluated by a monocyte-based target cell assay: identification of interleukin-10 as a major functional deactivator of human monocytes. Brandtzaeg, P., Osnes, L., Ovstebø, R., Joø, G.B., Westvik, A.B., Kierulf, P. J. Exp. Med. (1996) [Pubmed]
  16. Diverging signal transduction pathways activated by interleukin-8 and related chemokines in human neutrophils: interleukin-8, but not NAP-2 or GRO alpha, stimulates phospholipase D activity. L'Heureux, G.P., Bourgoin, S., Jean, N., McColl, S.R., Naccache, P.H. Blood (1995) [Pubmed]
  17. Presence of autoantibodies to interleukin-8 or neutrophil-activating peptide-2 in patients with heparin-associated thrombocytopenia. Amiral, J., Marfaing-Koka, A., Wolf, M., Alessi, M.C., Tardy, B., Boyer-Neumann, C., Vissac, A.M., Fressinaud, E., Poncz, M., Meyer, D. Blood (1996) [Pubmed]
  18. Novel mechanism of glucocorticoid-mediated gene repression. Nuclear factor-kappa B is target for glucocorticoid-mediated interleukin 8 gene repression. Mukaida, N., Morita, M., Ishikawa, Y., Rice, N., Okamoto, S., Kasahara, T., Matsushima, K. J. Biol. Chem. (1994) [Pubmed]
  19. Tumor necrosis factor alpha and interferon gamma synergistically induce interleukin 8 production in a human gastric cancer cell line through acting concurrently on AP-1 and NF-kB-like binding sites of the interleukin 8 gene. Yasumoto, K., Okamoto, S., Mukaida, N., Murakami, S., Mai, M., Matsushima, K. J. Biol. Chem. (1992) [Pubmed]
  20. Molecular evolution of the human interleukin-8 receptor gene cluster. Ahuja, S.K., Ozçelik, T., Milatovitch, A., Francke, U., Murphy, P.M. Nat. Genet. (1992) [Pubmed]
  21. Interleukin 10 (IL-10) inhibits the release of proinflammatory cytokines from human polymorphonuclear leukocytes. Evidence for an autocrine role of tumor necrosis factor and IL-1 beta in mediating the production of IL-8 triggered by lipopolysaccharide. Cassatella, M.A., Meda, L., Bonora, S., Ceska, M., Constantin, G. J. Exp. Med. (1993) [Pubmed]
  22. Molecular cloning of a human monocyte-derived neutrophil chemotactic factor (MDNCF) and the induction of MDNCF mRNA by interleukin 1 and tumor necrosis factor. Matsushima, K., Morishita, K., Yoshimura, T., Lavu, S., Kobayashi, Y., Lew, W., Appella, E., Kung, H.F., Leonard, E.J., Oppenheim, J.J. J. Exp. Med. (1988) [Pubmed]
  23. Effects of the neutrophil-activating peptide NAP-2, platelet basic protein, connective tissue-activating peptide III and platelet factor 4 on human neutrophils. Walz, A., Dewald, B., von Tscharner, V., Baggiolini, M. J. Exp. Med. (1989) [Pubmed]
  24. Activation of CD38 by interleukin-8 signaling regulates intracellular Ca2+ level and motility of lymphokine-activated killer cells. Rah, S.Y., Park, K.H., Han, M.K., Im, M.J., Kim, U.H. J. Biol. Chem. (2005) [Pubmed]
  25. The neutrophil-activating proteins interleukin 8 and beta-thromboglobulin: in vitro and in vivo comparison of NH2-terminally processed forms. Van Damme, J., Rampart, M., Conings, R., Decock, B., Van Osselaer, N., Willems, J., Billiau, A. Eur. J. Immunol. (1990) [Pubmed]
  26. Normal breast epithelial cells produce interleukins 6 and 8 together with tumor-necrosis factor: defective IL6 expression in mammary carcinoma. Basolo, F., Conaldi, P.G., Fiore, L., Calvo, S., Toniolo, A. Int. J. Cancer (1993) [Pubmed]
  27. Superinduction of interleukin 8 mRNA in activated monocyte derived macrophages from rheumatoid arthritis patients. Rodenburg, R.J., van Den Hoogen, F.H., Barrera, P., van Venrooij, W.J., van De Putte, L.B. Ann. Rheum. Dis. (1999) [Pubmed]
  28. Chemokine receptor-ligand interactions measured using time-resolved fluorescence. Inglese, J., Samama, P., Patel, S., Burbaum, J., Stroke, I.L., Appell, K.C. Biochemistry (1998) [Pubmed]
  29. Lipopolysaccharide-stimulated human monocytes secrete, apart from neutrophil-activating peptide 1/interleukin 8, a second neutrophil-activating protein. NH2-terminal amino acid sequence identity with melanoma growth stimulatory activity. Schröder, J.M., Persoon, N.L., Christophers, E. J. Exp. Med. (1990) [Pubmed]
  30. Palmitic acid induces production of proinflammatory cytokine interleukin-8 from hepatocytes. Joshi-Barve, S., Barve, S.S., Amancherla, K., Gobejishvili, L., Hill, D., Cave, M., Hote, P., McClain, C.J. Hepatology (2007) [Pubmed]
  31. Synergistic activation of interleukin-8 gene transcription by all-trans-retinoic acid and tumor necrosis factor-alpha involves the transcription factor NF-kappaB. Harant, H., de Martin, R., Andrew, P.J., Foglar, E., Dittrich, C., Lindley, I.J. J. Biol. Chem. (1996) [Pubmed]
  32. Melanoma growth-stimulatory activity/GRO decreases collagen expression by human fibroblasts. Regulation by C-X-C but not C-C cytokines. Unemori, E.N., Amento, E.P., Bauer, E.A., Horuk, R. J. Biol. Chem. (1993) [Pubmed]
  33. A molecular switch of chemokine receptor selectivity. Chemical modification of the interleukin-8 Leu25 --> Cys mutant. Lusti-Narasimhan, M., Chollet, A., Power, C.A., Allet, B., Proudfoot, A.E., Wells, T.N. J. Biol. Chem. (1996) [Pubmed]
  34. Identification of a potent, selective non-peptide CXCR2 antagonist that inhibits interleukin-8-induced neutrophil migration. White, J.R., Lee, J.M., Young, P.R., Hertzberg, R.P., Jurewicz, A.J., Chaikin, M.A., Widdowson, K., Foley, J.J., Martin, L.D., Griswold, D.E., Sarau, H.M. J. Biol. Chem. (1998) [Pubmed]
  35. The human erythrocyte inflammatory peptide (chemokine) receptor. Biochemical characterization, solubilization, and development of a binding assay for the soluble receptor. Horuk, R., Colby, T.J., Darbonne, W.C., Schall, T.J., Neote, K. Biochemistry (1993) [Pubmed]
  36. Efficiency of von Willebrand factor-mediated targeting of interleukin-8 into Weibel-Palade bodies. Bierings, R., van den Biggelaar, M., Kragt, A., Mertens, K., Voorberg, J., van Mourik, J.A. J. Thromb. Haemost. (2007) [Pubmed]
  37. The differential ability of IL-8 and neutrophil-activating peptide-2 to induce attenuation of chemotaxis is mediated by their divergent capabilities to phosphorylate CXCR2 (IL-8 receptor B). Ben-Baruch, A., Grimm, M., Bengali, K., Evans, G.A., Chertov, O., Wang, J.M., Howard, O.M., Mukaida, N., Matsushima, K., Oppenheim, J.J. J. Immunol. (1997) [Pubmed]
  38. Chemokine IL-8 induction by particulate wear debris in osteoblasts is mediated by NF-kappaB. Fritz, E.A., Jacobs, J.J., Glant, T.T., Roebuck, K.A. J. Orthop. Res. (2005) [Pubmed]
  39. Novel pathways of F-actin polymerization in the human neutrophil. Chodniewicz, D., Zhelev, D.V. Blood (2003) [Pubmed]
  40. Role of interleukin-8 phosphorylated kinases in stimulating neutrophil migration through fibrin gels. Schnyder, B., Bogdan, J.A., Schnyder-Candrian, S. Lab. Invest. (1999) [Pubmed]
  41. Interleukin 8 (IL-8) selectively inhibits immunoglobulin E production induced by IL-4 in human B cells. Kimata, H., Yoshida, A., Ishioka, C., Lindley, I., Mikawa, H. J. Exp. Med. (1992) [Pubmed]
  42. Interleukin-18 (IFNgamma-inducing factor) induces IL-8 and IL-1beta via TNFalpha production from non-CD14+ human blood mononuclear cells. Puren, A.J., Fantuzzi, G., Gu, Y., Su, M.S., Dinarello, C.A. J. Clin. Invest. (1998) [Pubmed]
  43. Interleukin 18 stimulates HIV type 1 in monocytic cells. Shapiro, L., Puren, A.J., Barton, H.A., Novick, D., Peskind, R.L., Shenkar, R., Gu, Y., Su, M.S., Dinarello, C.A. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  44. Interleukin-10 inhibits interleukin-8 production in human neutrophils. Wang, P., Wu, P., Anthes, J.C., Siegel, M.I., Egan, R.W., Billah, M.M. Blood (1994) [Pubmed]
  45. Effect of granulocyte-macrophage colony-stimulating factor and interleukin-3 on interleukin-8 production by human neutrophils and monocytes. Takahashi, G.W., Andrews, D.F., Lilly, M.B., Singer, J.W., Alderson, M.R. Blood (1993) [Pubmed]
  46. Role of the Jak/STAT pathway in the regulation of interleukin-8 transcription by oxidized phospholipids in vitro and in atherosclerosis in vivo. Gharavi, N.M., Alva, J.A., Mouillesseaux, K.P., Lai, C., Yeh, M., Yeung, W., Johnson, J., Szeto, W.L., Hong, L., Fishbein, M., Wei, L., Pfeffer, L.M., Berliner, J.A. J. Biol. Chem. (2007) [Pubmed]
  47. Oxidative inactivation of the proteasome in retinal pigment epithelial cells. A potential link between oxidative stress and up-regulation of interleukin-8. Fernandes, A.F., Zhou, J., Zhang, X., Bian, Q., Sparrow, J., Taylor, A., Pereira, P., Shang, F. J. Biol. Chem. (2008) [Pubmed]
  48. A highly selective CC chemokine receptor (CCR)8 antagonist encoded by the poxvirus molluscum contagiosum. Lüttichau, H.R., Stine, J., Boesen, T.P., Johnsen, A.H., Chantry, D., Gerstoft, J., Schwartz, T.W. J. Exp. Med. (2000) [Pubmed]
  49. Immunoregulatory role of interleukin 10 in rheumatoid arthritis. Katsikis, P.D., Chu, C.Q., Brennan, F.M., Maini, R.N., Feldmann, M. J. Exp. Med. (1994) [Pubmed]
  50. Enhanced interleukin-8 release and gene expression in macrophages after exposure to Mycobacterium tuberculosis and its components. Zhang, Y., Broser, M., Cohen, H., Bodkin, M., Law, K., Reibman, J., Rom, W.N. J. Clin. Invest. (1995) [Pubmed]
  51. Differential cytokine expression by human intestinal epithelial cell lines: regulated expression of interleukin 8. Eckmann, L., Jung, H.C., Schürer-Maly, C., Panja, A., Morzycka-Wroblewska, E., Kagnoff, M.F. Gastroenterology (1993) [Pubmed]
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