interleukin 8a receptors

Summary

Summary: High-affinity G-protein-coupled receptors for INTERLEUKIN-8 present on NEUTROPHILS; MONOCYTES; and BASOPHILS.

Top Publications

  1. Godaly G, Hang L, Frendeus B, Svanborg C. Transepithelial neutrophil migration is CXCR1 dependent in vitro and is defective in IL-8 receptor knockout mice. J Immunol. 2000;165:5287-94 pubmed
    ..Furthermore, we show that CXCR1 is required for neutrophil migration across infected epithelial cell layers in vitro, and that the murine IL-8 receptor is needed for neutrophils to cross the infected mucosa of the urinary tract in vivo. ..
  2. Pease J, Sabroe I. The role of interleukin-8 and its receptors in inflammatory lung disease: implications for therapy. Am J Respir Med. 2002;1:19-25 pubmed
    ..Clinical trials of such compounds will ultimately provide crucial information currently lacking and will define whether or not IL-8 blockade provides future therapy in pulmonary disease. ..
  3. Bates R, DeLeo M, Mercurio A. The epithelial-mesenchymal transition of colon carcinoma involves expression of IL-8 and CXCR-1-mediated chemotaxis. Exp Cell Res. 2004;299:315-24 pubmed
    ..These studies establish that the regulated expression of a specific chemokine and its receptor are linked to the EMT and they provide a biochemical framework for understanding the mechanisms by which the EMT promotes migration. ..
  4. Bertini R, Allegretti M, Bizzarri C, Moriconi A, Locati M, Zampella G, et al. Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury. Proc Natl Acad Sci U S A. 2004;101:11791-6 pubmed
    ..Targeting the Repertaxin interaction site of CXCR1 represents a general strategy to modulate the activity of chemoattractant receptors. ..
  5. Qiu Y, Zhu J, Bandi V, Atmar R, Hattotuwa K, Guntupalli K, et al. Biopsy neutrophilia, neutrophil chemokine and receptor gene expression in severe exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2003;168:968-75 pubmed
    ..Thus, in COPD, in addition to CXCL8 and CXCR1, CXCL5 and CXCR2 appear to play important roles in the airway neutrophilia characteristic of severe exacerbations. ..
  6. Li A, Varney M, Singh R. Expression of interleukin 8 and its receptors in human colon carcinoma cells with different metastatic potentials. Clin Cancer Res. 2001;7:3298-304 pubmed
  7. Godaly G, Proudfoot A, Offord R, Svanborg C, Agace W. Role of epithelial interleukin-8 (IL-8) and neutrophil IL-8 receptor A in Escherichia coli-induced transuroepithelial neutrophil migration. Infect Immun. 1997;65:3451-6 pubmed
    ..These results demonstrate that IL-8 plays a key role in E. coli- or IL-1alpha-induced transuroepithelial migration and suggest that epithelial cell-produced IL-8 interacts with IL-8RA on the neutrophil surface. ..
  8. Lee J, Horuk R, Rice G, Bennett G, Camerato T, Wood W. Characterization of two high affinity human interleukin-8 receptors. J Biol Chem. 1992;267:16283-7 pubmed
  9. Brat D, Bellail A, Van Meir E. The role of interleukin-8 and its receptors in gliomagenesis and tumoral angiogenesis. Neuro Oncol. 2005;7:122-33 pubmed
    ..A precise definition of the mechanisms by which IL-8 exerts its proangiogenic functions requires further study for the development of effective IL-8-targeted therapies. ..

More Information

Publications62

  1. Ahuja S, Ozcelik T, Milatovitch A, Francke U, Murphy P. Molecular evolution of the human interleukin-8 receptor gene cluster. Nat Genet. 1992;2:31-6 pubmed
  2. Mueller S, Schraw W, Richmond A. Melanoma growth stimulatory activity enhances the phosphorylation of the class II interleukin-8 receptor in non-hematopoietic cells. J Biol Chem. 1994;269:1973-80 pubmed
    ..Phosphoamino acid analysis indicated that the MGSA-induced receptor phosphorylation was on serine residue(s), suggesting that a serine kinase is activated in response to MGSA binding to the class II IL-8R in non-hematopoietic cells. ..
  3. Holmes W, Lee J, Kuang W, Rice G, Wood W. Structure and functional expression of a human interleukin-8 receptor. Science. 1991;253:1278-80 pubmed
    ..The IL-8 receptor may be part of a subfamily of related G protein-coupled receptors that transduce signals for the IL-8 family of pro-inflammatory cytokines. ..
  4. Ginestier C, Liu S, Diebel M, Korkaya H, Luo M, Brown M, et al. CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J Clin Invest. 2010;120:485-97 pubmed publisher
    ..Our data therefore suggest that CXCR1 blockade may provide a novel means of targeting and eliminating breast CSCs. ..
  5. Masood R, Cai J, Tulpule A, Zheng T, Hamilton A, Sharma S, et al. Interleukin 8 is an autocrine growth factor and a surrogate marker for Kaposi's sarcoma. Clin Cancer Res. 2001;7:2693-702 pubmed
    ..Serum levels of IL-8 were also elevated in KS cases compared with matched controls. Modulation of IL-8 may thus be of therapeutic value in this disease. ..
  6. Murphy P, Tiffany H. Cloning of complementary DNA encoding a functional human interleukin-8 receptor. Science. 1991;253:1280-3 pubmed
  7. Lloyd A, Modi W, Sprenger H, Cevario S, Oppenheim J, Kelvin D. Assignment of genes for interleukin-8 receptors (IL8R) A and B to human chromosome band 2q35. Cytogenet Cell Genet. 1993;63:238-40 pubmed
    ..The IL8R genes were further localized by in situ hybridization to band 2q35. ..
  8. Damaj B, McColl S, Mahana W, Crouch M, Naccache P. Physical association of Gi2alpha with interleukin-8 receptors. J Biol Chem. 1996;271:12783-9 pubmed
    ..Finally, the results of this study also validate the use of the transfected 293 cell line as a model for the study of the signal transduction pathway(s) initiated by IL-8. ..
  9. Govindaraju V, Michoud M, Al Chalabi M, Ferraro P, Powell W, Martin J. Interleukin-8: novel roles in human airway smooth muscle cell contraction and migration. Am J Physiol Cell Physiol. 2006;291:C957-65 pubmed
    ..These data suggest a potential role for IL-8 in causing abnormal airway structure and function in asthma and CF. ..
  10. Svanborg C, Bergsten G, Fischer H, Godaly G, Gustafsson M, Karpman D, et al. Uropathogenic Escherichia coli as a model of host-parasite interaction. Curr Opin Microbiol. 2006;9:33-9 pubmed
    ..CXCR1 mutant mice become bacteremic and develop renal scars and studies in UTI prone children have detected low CXCR1 expression, suggesting that CXCR1 is also essential for human disease susceptibility. ..
  11. Li A, Varney M, Valasek J, Godfrey M, Dave B, Singh R. Autocrine role of interleukin-8 in induction of endothelial cell proliferation, survival, migration and MMP-2 production and angiogenesis. Angiogenesis. 2005;8:63-71 pubmed
    ..Together these data suggest that IL-8 functions as an important autocrine growth and angiogenic factor in regulating multiple biological activities in endothelial cells. ..
  12. Balish E, Wagner R, Vazquez Torres A, Jones Carson J, Pierson C, Warner T. Mucosal and systemic candidiasis in IL-8Rh-/- BALB/c mice. J Leukoc Biol. 1999;66:144-50 pubmed
    ..These results suggest a role for the IL-8Rh in murine resistance to gastric and acute systemic candidiasis, but not in resistance to systemic candidiasis of endogenous origin. ..
  13. Schonbeck U, Brandt E, Petersen F, Flad H, Loppnow H. IL-8 specifically binds to endothelial but not to smooth muscle cells. J Immunol. 1995;154:2375-83 pubmed
    ..The differential capacity of EC and SMC to produce IL-8 and express IL-8 binding sites indicates that vascular cell-derived IL-8 may contribute to differential regulation of infectious and inflammatory responses in the vessel wall. ..
  14. Zhu Y, Webster S, Flower D, Woll P. Interleukin-8/CXCL8 is a growth factor for human lung cancer cells. Br J Cancer. 2004;91:1970-6 pubmed
    ..In conclusion, IL-8 can act as an autocrine and/or paracrine growth factor for lung cancer cells, and the mitogenic function of IL-8 in lung cancer is mediated mainly by CXCR1 receptor. ..
  15. Richardson R, Ali H, Pridgen B, Haribabu B, Snyderman R. Multiple signaling pathways of human interleukin-8 receptor A. Independent regulation by phosphorylation. J Biol Chem. 1998;273:10690-5 pubmed
    ..Since phosphorylation of CXCR1 had no effect on its ability to induce phosphorylation of PLCbeta3 or to mediate class-desensitization, these activities may be mediated by independently regulated pathways. ..
  16. Frendeus B, Godaly G, Hang L, Karpman D, Lundstedt A, Svanborg C. Interleukin 8 receptor deficiency confers susceptibility to acute experimental pyelonephritis and may have a human counterpart. J Exp Med. 2000;192:881-90 pubmed
    ..The results provide a first molecular clue to disease susceptibility of patients prone to acute pyelonephritis. ..
  17. Prado G, Suetomi K, Shumate D, Maxwell C, Ravindran A, Rajarathnam K, et al. Chemokine signaling specificity: essential role for the N-terminal domain of chemokine receptors. Biochemistry. 2007;46:8961-8 pubmed
    ..Thus, the diversity and intensity of inflammatory and noninflammatory responses mediated by chemokine receptors appear to be primarily determined by the initial interaction between the receptor N-terminus and the N-loop of chemokines. ..
  18. Wolf M, Delgado M, Jones S, Dewald B, Clark Lewis I, Baggiolini M. Granulocyte chemotactic protein 2 acts via both IL-8 receptors, CXCR1 and CXCR2. Eur J Immunol. 1998;28:164-70 pubmed
    ..Activation of CXCR1 appears to depend significantly on the presence of a basic binding determinant close to the second cysteine. ..
  19. Svensson M, Irjala H, Alm P, Holmqvist B, Lundstedt A, Svanborg C. Natural history of renal scarring in susceptible mIL-8Rh-/- mice. Kidney Int. 2005;67:103-10 pubmed
    ..The tissue damage resembles human disease, and these mice offer a model system to study the molecular mechanisms of renal scarring. ..
  20. Ahuja S, Shetty A, Tiffany H, Murphy P. Comparison of the genomic organization and promoter function for human interleukin-8 receptors A and B. J Biol Chem. 1994;269:26381-9 pubmed
    ..Thus, despite marked differences in the complexity of their genomic organization, il8ra and il8rb encode products that are similar in structure, function, and the major cell type of expression. ..
  21. Varney M, Johansson S, Singh R. Distinct expression of CXCL8 and its receptors CXCR1 and CXCR2 and their association with vessel density and aggressiveness in malignant melanoma. Am J Clin Pathol. 2006;125:209-16 pubmed
    ..Consistent with the transition from radial to vertical growth phase melanoma, expression of CXCL8 and its receptor, CXCR2, may be key in the switch to an aggressive, more metastatic phenotype. ..
  22. Varney M, Li A, Dave B, Bucana C, Johansson S, Singh R. Expression of CXCR1 and CXCR2 receptors in malignant melanoma with different metastatic potential and their role in interleukin-8 (CXCL-8)-mediated modulation of metastatic phenotype. Clin Exp Metastasis. 2003;20:723-31 pubmed
    ..In summary, the data suggest that constitutive expression of CXCR1 and CXCR2 play an important role regulating the IL-8-mediated metastatic phenotype in human malignant melanoma cells. ..
  23. Schraufstatter I, Chung J, Burger M. IL-8 activates endothelial cell CXCR1 and CXCR2 through Rho and Rac signaling pathways. Am J Physiol Lung Cell Mol Physiol. 2001;280:L1094-103 pubmed
    ..The retraction of endothelial cells due to activation of the CXCR2 may contribute to the increased vascular permeability observed in acute inflammation and during the angiogenic response...
  24. Artifoni L, Negrisolo S, Montini G, Zucchetta P, Molinari P, Cassar W, et al. Interleukin-8 and CXCR1 receptor functional polymorphisms and susceptibility to acute pyelonephritis. J Urol. 2007;177:1102-6 pubmed
    ..These data suggest that the gene for the proinflammatory chemokine interleukin-8 is involved in susceptibility to acute pyelonephritis during upper urinary tract infection in children with or without vesicoureteral reflux. ..
  25. Murphy C, McGurk M, Pettigrew J, Santinelli A, Mazzucchelli R, Johnston P, et al. Nonapical and cytoplasmic expression of interleukin-8, CXCR1, and CXCR2 correlates with cell proliferation and microvessel density in prostate cancer. Clin Cancer Res. 2005;11:4117-27 pubmed
  26. Lee J, Cacalano G, Camerato T, Toy K, Moore M, Wood W. Chemokine binding and activities mediated by the mouse IL-8 receptor. J Immunol. 1995;155:2158-64 pubmed
    ..These results show that macrophage inflammatory protein 2 and KC potently activate mouse neutrophils via a unique IL-8R, and these proteins may function as the major proinflammatory alpha chemokines in mice. ..
  27. Li A, Dubey S, Varney M, Dave B, Singh R. IL-8 directly enhanced endothelial cell survival, proliferation, and matrix metalloproteinases production and regulated angiogenesis. J Immunol. 2003;170:3369-76 pubmed
    ..Our data suggest that IL-8 directly enhanced endothelial cell proliferation, survival, and MMP expression in CXCR1- and CXCR2-expressing endothelial cells and regulated angiogenesis. ..
  28. Ramjeesingh R, Leung R, Siu C. Interleukin-8 secreted by endothelial cells induces chemotaxis of melanoma cells through the chemokine receptor CXCR1. FASEB J. 2003;17:1292-4 pubmed
    ..Antibodies against either IL-8 or CXCR1 inhibit melanoma transendothelial migration in a coculture assay by 30%. These results are consistent with a role for IL-8-induced chemotaxis in the transendothelial migration of melanoma cells. ..
  29. Sprenger H, Lloyd A, Meyer R, Johnston J, Kelvin D. Genomic structure, characterization, and identification of the promoter of the human IL-8 receptor A gene. J Immunol. 1994;153:2524-32 pubmed
    ..In conclusion, cloning a full-length cDNA permitted us to clone the human IL-8RA gene, identify the genomic structure, and characterize the promoter region. ..
  30. Li A, Dubey S, Varney M, Singh R. Interleukin-8-induced proliferation, survival, and MMP production in CXCR1 and CXCR2 expressing human umbilical vein endothelial cells. Microvasc Res. 2002;64:476-81 pubmed
  31. Smithson A, Sarrias M, Barcelo J, Suarez B, Horcajada J, Soto S, et al. Expression of interleukin-8 receptors (CXCR1 and CXCR2) in premenopausal women with recurrent urinary tract infections. Clin Diagn Lab Immunol. 2005;12:1358-63 pubmed
    ..These results suggest that a low level of CXCR2 expression may increase the susceptibilities of premenopausal women to urinary tract infections. ..
  32. Lundstedt A, Leijonhufvud I, Ragnarsdottir B, Karpman D, Andersson B, Svanborg C. Inherited susceptibility to acute pyelonephritis: a family study of urinary tract infection. J Infect Dis. 2007;195:1227-34 pubmed
    ..0001). Our results suggest that susceptibility to APN is inherited and that low CXCR1 expression might predispose to disease. ..
  33. Salcedo R, Resau J, Halverson D, Hudson E, Dambach M, Powell D, et al. Differential expression and responsiveness of chemokine receptors (CXCR1-3) by human microvascular endothelial cells and umbilical vein endothelial cells. FASEB J. 2000;14:2055-64 pubmed
    ..Whether this heterogeneity in receptor expression by ECs reflects distinct differentiation pathways remains to be established. ..
  34. Svanborg C, Bergsten G, Fischer H, Frendeus B, Godaly G, Gustafsson E, et al. The 'innate' host response protects and damages the infected urinary tract. Ann Med. 2001;33:563-70 pubmed
    ..Our studies hold the promise to provide a molecular and genetic explanation for disease susceptibility in some patients with UTI and to offer more precise tools for the diagnosis and therapy of these infections. ..
  35. Lundstedt A, McCarthy S, Gustafsson M, Godaly G, Jodal U, Karpman D, et al. A genetic basis of susceptibility to acute pyelonephritis. PLoS ONE. 2007;2:e825 pubmed
    ..0001) and two sequence variants were shown to impair transcription. The results identify a genetic innate immune deficiency, with a strong link to APN and renal scarring. ..
  36. Qiao H, Sonoda K, Ariyama A, Kuratomi Y, Kawano Y, Ishibashi T. CXCR2 Expression on neutrophils is upregulated during the relapsing phase of ocular Behcet disease. Curr Eye Res. 2005;30:195-203 pubmed
    ..Importantly, low-dose prednisolone therapy reduced CXCR2 expression on neutrophils. CXCR2 has a potential role in promot-ing uveitis during ocular attack and might also be a useful marker for disease activity. ..
  37. Ramirez B, Howard O, Dong H, Edamatsu T, Gao P, Hartlein M, et al. Brugia malayi asparaginyl-transfer RNA synthetase induces chemotaxis of human leukocytes and activates G-protein-coupled receptors CXCR1 and CXCR2. J Infect Dis. 2006;193:1164-71 pubmed
    ..Our findings suggest that a filarial parasite chemoattractant protein may contribute to the development of chronic inflammatory disease and that chemokine receptors may be therapeutic targets to ameliorate parasite-induced pathology. ..
  38. Pignatti P, Moscato G, Casarini S, Delmastro M, Poppa M, Brunetti G, et al. Downmodulation of CXCL8/IL-8 receptors on neutrophils after recruitment in the airways. J Allergy Clin Immunol. 2005;115:88-94 pubmed
    ..The downmodulation of CXCL8/IL-8 receptors detected in the airways should be taken into account for an eventual therapeutic inhibition of these receptors. ..
  39. Li H, Nord E. IL-8 amplifies CD40/CD154-mediated ICAM-1 production via the CXCR-1 receptor and p38-MAPK pathway in human renal proximal tubule cells. Am J Physiol Renal Physiol. 2009;296:F438-45 pubmed publisher
    ..This cascade of events is independent of CD40/CD154-mediated IL-8 stimulation and ICAM-1 production and serves to amplify the inflammatory response. ..
  40. Pay S, Musabak U, Simsek I, Pekel A, Erdem H, Dinc A, et al. Expression of CXCR-1 and CXCR-2 chemokine receptors on synovial neutrophils in inflammatory arthritides: does persistent or increasing expression of CXCR-2 contribute to the chronic inflammation or erosive changes?. Joint Bone Spine. 2006;73:691-6 pubmed
    ..These results indicate that CXCR-2 chemokine receptor might play more critical role in long lasting accumulation of neutrophils within the synovial fluid of patients with RA. ..
  41. Ulukus M, Ulukus E, Seval Y, Cinar O, Zheng W, Arici A. Expression of interleukin-8 receptors in patients with adenomyosis. Fertil Steril. 2006;85:714-20 pubmed
    ..These findings suggest that IL-8 receptors may be involved in the pathogenesis and/or pathophysiology of adenomyosis. ..
  42. Almeida M, Cordero M, Almeida J, Orfao A. Different subsets of peripheral blood dendritic cells show distinct phenotypic and functional abnormalities in HIV-1 infection. AIDS. 2005;19:261-71 pubmed
  43. Lin B, Chang C, Chen L, Wu M, Wang M, Kuo I, et al. Cysteine-rich 61 (CCN1) enhances chemotactic migration, transendothelial cell migration, and intravasation by concomitantly up-regulating chemokine receptor 1 and 2. Mol Cancer Res. 2007;5:1111-23 pubmed
    ..In conclusion, we suggest that Cyr61 promotes interleukin-8-dependent chemotaxis, transendothelial migration, and intravasation by induction of CXCR1/CXCR2 through integrin alphavbeta3/Src/PI3K/Akt-dependent pathway. ..
  44. Capsoni F, Ongari A, Frigerio E, Taglioni M, Altomare G. Effect of Efalizumab on neutrophil and monocyte functions in patients with psoriasis. Int J Immunopathol Pharmacol. 2008;21:437-45 pubmed
    ..Our findings suggest that neutrophils and monocytes may be among the targets of efalizumab activity in patients with psoriasis. ..
  45. Huber T, Reinhardt H, Exner M, Burger J, Kerjaschki D, Saleem M, et al. Expression of functional CCR and CXCR chemokine receptors in podocytes. J Immunol. 2002;168:6244-52 pubmed
    ..The release of oxygen radicals that accompanies the activation of CCRs and CXCRs may contribute to podocyte injury and the development of proteinuria during membranous nephropathy. ..
  46. Zambello R, Trentin L, Facco M, Carollo D, Cabrelle A, Tosoni A, et al. Upregulation of CXCR1 by proliferating cells in patients with lymphoproliferative disease of granular lymphocytes. Br J Haematol. 2003;120:765-73 pubmed
  47. Huynh N, Mallik B, Zhang L, Martins Green M, Morikis D. Computational studies of CXCR1, the receptor of IL-8/CXCL8, using molecular dynamics and electrostatics. Biopolymers. 2008;89:52-61 pubmed
  48. Singh S, Sadanandam A, Varney M, Nannuru K, Singh R. Small interfering RNA-mediated CXCR1 or CXCR2 knock-down inhibits melanoma tumor growth and invasion. Int J Cancer. 2010;126:328-36 pubmed publisher
  49. Nirodi C, Hart J, Dhawan P, Moon N, Nepveu A, Richmond A. The role of CDP in the negative regulation of CXCL1 gene expression. J Biol Chem. 2001;276:26122-31 pubmed
    ..Based on these results, we propose that transcriptional regulation of the CXCL1 gene is mediated in part by CDP, which could play an important role in inflammatory processes and tumorigenesis. ..
  50. Nishi T, Takeuchi H, Matsuda S, Ogura M, Kawakubo H, Fukuda K, et al. CXCR2 expression and postoperative complications affect long-term survival in patients with esophageal cancer. World J Surg Oncol. 2015;13:232 pubmed publisher
    ..This study was approved by Keio University School of Medicine Ethics Committee with a trial registration number of 2011-241. ..
  51. Gonsiorek W, Fan X, Hesk D, Fossetta J, Qiu H, Jakway J, et al. Pharmacological characterization of Sch527123, a potent allosteric CXCR1/CXCR2 antagonist. J Pharmacol Exp Ther. 2007;322:477-85 pubmed
    ..049 +/- 0.004 nM). Taken together, our data show that Sch527123 represents a novel, potent, and specific CXCR2 antagonist with potential therapeutic utility in a variety of inflammatory conditions. ..
  52. Salim J, Goette N, Lev P, Chazarreta C, Heller P, Alvarez C, et al. Dysregulation of stromal derived factor 1/CXCR4 axis in the megakaryocytic lineage in essential thrombocythemia. Br J Haematol. 2009;144:69-77 pubmed publisher
  53. Shih C, Chiang T, Wang W. Synergistic suppression of a disintegrin acurhagin-C in combination with AZD4547 and reparixin on terminating development for human osteosarcoma MG-63 cell. Biochem Biophys Res Commun. 2017;492:513-519 pubmed publisher
    ..These data supported an ECD-disintegrin acurhagin-C targeting integrin-?5 upon combined used with AZD4547 and reparixin may become a promising therapeutic approach for attenuating osteosarcoma development. ..