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Gene Review

CXCR2  -  chemokine (C-X-C motif) receptor 2

Homo sapiens

Synonyms: C-X-C chemokine receptor type 2, CD182, CDw128b, CMKAR2, CXC-R2, ...
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Disease relevance of IL8RB


Psychiatry related information on IL8RB

  • Immunohistochemical analysis of the involved brain tissues from patients with Alzheimer's disease revealed expression of CXCR2 in the neuritic portion of plaques surrounding deposits of amyloid [7].

High impact information on IL8RB


Chemical compound and disease context of IL8RB

  • Moreover, treatment with anti-mouse CXCR-2-neutralizing Ab significantly attenuated the growth of both neomycin phosphotransferase gene-transfected and IL-17-transfected NSCLC tumors in SCID mice [12].
  • In contrast, membranous expression of IL-8, CXCR1, and CXCR2 was nonapical in cancer cells of Gleason pattern 3 and 4, whereas circumferential expression was present in Gleason pattern 5 and androgen-independent prostate cancer [13].
  • In whole blood in vitro, LPS, lipoarabinomannan from Mycobacterium tuberculosis, and lipoteichoic acid from Staphylococcus aureus reduced expression of CXCR2 but not of CXCR1 [14].
  • Competitive inhibition of the IL-8 receptor CXCR2 with the small molecule inhibitor SB225002 resulted in a 45-70% decrease in cervical explant susceptibility to HIV-1 infection [15].
  • Pretreatment of monocytes with scavenger receptor inhibitors, polyinosinic acid (100 microg/ml) and dextran sulfate (50 microg/ml) attenuated CXCR2 expression, but pertussis toxin or cholera toxin had no effect [16].

Biological context of IL8RB


Anatomical context of IL8RB

  • The levels of CXCR1 and CXCR2 mRNA were constant during phagocytic stimulation of neutrophils [21].
  • This potentiation correlated with enhanced binding to neutrophils and increased signaling through CXC chemokine receptor-1 (CXCR1), but it was significantly less pronounced on a CXCR2-expressing cell line [22].
  • Furthermore, our results suggest that rab11(+)-endosomes participate in the trafficking of CXCR2 through the endocytic pathway, to eventually allow its recycling back to the plasma membrane [2].
  • Moreover, addition of neutralizing anti-IL-8 receptor (CXC chemokine receptor 1 [CXCR1] or 2 [CXCR2]) antibodies to MMM CD34+ cells cultured under MK liquid culture conditions increases the proliferation and differentiation of MMM CD41+ MK cells and restores their polyploidization [3].
  • IL-8 elicits angiogenic responses in microvascular endothelial cells isolated from human intestine by engaging CXCR2 [23].

Associations of IL8RB with chemical compounds

  • When CXCR2 was expressed with the AMPA-type glutamate receptor GluR1, CXCR2 dimerization was again impaired in a dose-dependent way, and receptor functions were prejudiced [19].
  • These data demonstrate for the first time that ligand binding to CXCR2 results in receptor phosphorylation, desensitization, and sequestration and that serine residues 342 and 346-348 participate in the desensitization and sequestration processes [24].
  • These results show that CXCR2 selective receptor antagonists can be generated based upon the secondary binding determinants of GROalpha and PF4 [25].
  • Chemokine antagonists that discriminate between interleukin-8 receptors. Selective blockers of CXCR2 [25].
  • A typical expression pattern for IL-8 receptor A was detected, with expression only on the luminal side of the epithelial tumor cells, while IL-8 receptor B was more evenly distributed in the tissue [26].

Physical interactions of IL8RB

  • Interleukin 8, neutrophil-activating peptide-2 and GRO-alpha bind to and elicit cell activation via specific and different amino acid residues of CXCR2 [27].
  • The LL320,321AA, IL323,324AA, and LLIL320,321,323,324AAAA mutants of CXCR2 exhibit normal binding to beta-arrestin 1 but exhibit decreased binding to adaptin 2alpha and beta [28].

Enzymatic interactions of IL8RB

  • Interestingly, CCR1 cross-phosphorylated and cross-desensitized CXCR2, but not CXCR1 [18].
  • 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) [29].

Regulatory relationships of IL8RB

  • The present findings suggest that CXCR2 is responsible for neutrophil chemotaxis and margination induced by IL-8 [20].
  • To conclude, our findings shed light on the interrelationships between GCP-2 and other ELR(+)-CXC chemokines, and determine the mechanisms involved in the regulation of GCP-2-induced internalization and recycling of CXCR2 [2].
  • Sufficient stimulation of the CXCR1 terminated this cooperative relationship by downregulating surface expression of CXCR2 [30].
  • Furthermore, inhibition of the EGFR also attenuated focus formation in NIH 3T3 expressing the CXCR2 [31].
  • CCR3 antagonists (which block eosinophil chemotaxis) and CXCR2 antagonists (which block neutrophil and monocyte chemotaxis) are in clinical development for asthma and COPD, respectively [32].

Other interactions of IL8RB

  • Regulation of the human chemokine receptor CCR1. Cross-regulation by CXCR1 and CXCR2 [18].
  • This derivative was ineffective on CXCR1, but was as active as wild-type GCP-2 in CXCR2-expressing cells [33].
  • Thus, positive association with SLC11A1 should be interpreted cautiously, and IL8RB should also be considered as a potential candidate susceptibility gene unless proven otherwise [34].
  • Among KSHV-seropositive Italians, CKS risk was associated with diplotypes of IL8RB and IL13, supporting laboratory evidence of immune-mediated pathogenesis [35].
  • A novel flow cytometric assay of human whole blood neutrophil and monocyte CD11b levels: upregulation by chemokines is related to receptor expression, comparison with neutrophil shape change, and effects of a chemokine receptor (CXCR2) antagonist [36].

Analytical, diagnostic and therapeutic context of IL8RB


  1. Variants of the IL8 and IL8RB genes and risk for gastric cardia adenocarcinoma and esophageal squamous cell carcinoma. Savage, S.A., Abnet, C.C., Mark, S.D., Qiao, Y.L., Dong, Z.W., Dawsey, S.M., Taylor, P.R., Chanock, S.J. Cancer Epidemiol. Biomarkers Prev. (2004) [Pubmed]
  2. GCP-2-induced internalization of IL-8 receptors: hierarchical relationships between GCP-2 and other ELR(+)-CXC chemokines and mechanisms regulating CXCR2 internalization and recycling. Feniger-Barish, R., Belkin, D., Zaslaver, A., Gal, S., Dori, M., Ran, M., Ben-Baruch, A. Blood (2000) [Pubmed]
  3. IL-8 and its CXCR1 and CXCR2 receptors participate in the control of megakaryocytic proliferation, differentiation, and ploidy in myeloid metaplasia with myelofibrosis. Emadi, S., Clay, D., Desterke, C., Guerton, B., Maquarre, E., Charpentier, A., Jasmin, C., Le Bousse-Kerdilès, M.C. Blood (2005) [Pubmed]
  4. Chemokine receptors CXCR-1/2 activate mitogen-activated protein kinase via the epidermal growth factor receptor in ovarian cancer cells. Venkatakrishnan, G., Salgia, R., Groopman, J.E. J. Biol. Chem. (2000) [Pubmed]
  5. Biopsy neutrophilia, neutrophil chemokine and receptor gene expression in severe exacerbations of chronic obstructive pulmonary disease. Qiu, Y., Zhu, J., Bandi, V., Atmar, R.L., Hattotuwa, K., Guntupalli, K.K., Jeffery, P.K. Am. J. Respir. Crit. Care Med. (2003) [Pubmed]
  6. CXCR2 promotes ovarian cancer growth through dysregulated cell cycle, diminished apoptosis, and enhanced angiogenesis. Yang, G., Rosen, D.G., Liu, G., Yang, F., Guo, X., Xiao, X., Xue, F., Mercado-Uribe, I., Huang, J., Lin, S.H., Mills, G.B., Liu, J. Clin. Cancer Res. (2010) [Pubmed]
  7. Expression of chemokine receptors by subsets of neurons in the central nervous system. Horuk, R., Martin, A.W., Wang, Z., Schweitzer, L., Gerassimides, A., Guo, H., Lu, Z., Hesselgesser, J., Perez, H.D., Kim, J., Parker, J., Hadley, T.J., Peiper, S.C. J. Immunol. (1997) [Pubmed]
  8. The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. Tsai, H.H., Frost, E., To, V., Robinson, S., Ffrench-Constant, C., Geertman, R., Ransohoff, R.M., Miller, R.H. Cell (2002) [Pubmed]
  9. 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]
  10. A novel peptide CXCR ligand derived from extracellular matrix degradation during airway inflammation. Weathington, N.M., van Houwelingen, A.H., Noerager, B.D., Jackson, P.L., Kraneveld, A.D., Galin, F.S., Folkerts, G., Nijkamp, F.P., Blalock, J.E. Nat. Med. (2006) [Pubmed]
  11. 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]
  12. IL-17 enhances the net angiogenic activity and in vivo growth of human non-small cell lung cancer in SCID mice through promoting CXCR-2-dependent angiogenesis. Numasaki, M., Watanabe, M., Suzuki, T., Takahashi, H., Nakamura, A., McAllister, F., Hishinuma, T., Goto, J., Lotze, M.T., Kolls, J.K., Sasaki, H. J. Immunol. (2005) [Pubmed]
  13. Nonapical and cytoplasmic expression of interleukin-8, CXCR1, and CXCR2 correlates with cell proliferation and microvessel density in prostate cancer. Murphy, C., McGurk, M., Pettigrew, J., Santinelli, A., Mazzucchelli, R., Johnston, P.G., Montironi, R., Waugh, D.J. Clin. Cancer Res. (2005) [Pubmed]
  14. Expression of the chemokine receptors CXCR1 and CXCR2 on granulocytes in human endotoxemia and tuberculosis: involvement of the p38 mitogen-activated protein kinase pathway. Juffermans, N.P., Dekkers, P.E., Peppelenbosch, M.P., Speelman, P., van Deventer, S.J., van Der Poll, T. J. Infect. Dis. (2000) [Pubmed]
  15. IL-8 increases transmission of HIV type 1 in cervical explant tissue. Narimatsu, R., Wolday, D., Patterson, B.K. AIDS Res. Hum. Retroviruses (2005) [Pubmed]
  16. OxLDL upregulates CXCR2 expression in monocytes via scavenger receptors and activation of p38 mitogen-activated protein kinase. Lei, Z.B., Zhang, Z., Jing, Q., Qin, Y.W., Pei, G., Cao, B.Z., Li, X.Y. Cardiovasc. Res. (2002) [Pubmed]
  17. The CXC-chemokine neutrophil-activating peptide-2 induces two distinct optima of neutrophil chemotaxis by differential interaction with interleukin-8 receptors CXCR-1 and CXCR-2. Ludwig, A., Petersen, F., Zahn, S., Götze, O., Schröder, J.M., Flad, H.D., Brandt, E. Blood (1997) [Pubmed]
  18. Regulation of the human chemokine receptor CCR1. Cross-regulation by CXCR1 and CXCR2. Richardson, R.M., Pridgen, B.C., Haribabu, B., Snyderman, R. J. Biol. Chem. (2000) [Pubmed]
  19. Ligand-independent CXCR2 dimerization. Trettel, F., Di Bartolomeo, S., Lauro, C., Catalano, M., Ciotti, M.T., Limatola, C. J. Biol. Chem. (2003) [Pubmed]
  20. 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]
  21. Phagocytosing neutrophils down-regulate the expression of chemokine receptors CXCR1 and CXCR2. Doroshenko, T., Chaly, Y., Savitskiy, V., Maslakova, O., Portyanko, A., Gorudko, I., Voitenok, N.N. Blood (2002) [Pubmed]
  22. 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. Van den Steen, P.E., Proost, P., Wuyts, A., Van Damme, J., Opdenakker, G. Blood (2000) [Pubmed]
  23. Angiogenic effects of interleukin 8 (CXCL8) in human intestinal microvascular endothelial cells are mediated by CXCR2. Heidemann, J., Ogawa, H., Dwinell, M.B., Rafiee, P., Maaser, C., Gockel, H.R., Otterson, M.F., Ota, D.M., Lugering, N., Domschke, W., Binion, D.G. J. Biol. Chem. (2003) [Pubmed]
  24. Ligand-induced desensitization of the human CXC chemokine receptor-2 is modulated by multiple serine residues in the carboxyl-terminal domain of the receptor. Mueller, S.G., White, J.R., Schraw, W.P., Lam, V., Richmond, A. J. Biol. Chem. (1997) [Pubmed]
  25. Chemokine antagonists that discriminate between interleukin-8 receptors. Selective blockers of CXCR2. Jones, S.A., Dewald, B., Clark-Lewis, I., Baggiolini, M. J. Biol. Chem. (1997) [Pubmed]
  26. Upregulation of interleukin-8 and polarized epithelial expression of interleukin-8 receptor A in ovarian carcinomas. Ivarsson, K., Ekerydh, A., Fyhr, I.M., Janson, P.O., Brännström, M. Acta obstetricia et gynecologica Scandinavica. (2000) [Pubmed]
  27. Interleukin 8, neutrophil-activating peptide-2 and GRO-alpha bind to and elicit cell activation via specific and different amino acid residues of CXCR2. Katancik, J.A., Sharma, A., de Nardin, E. Cytokine (2000) [Pubmed]
  28. Identification of a motif in the carboxyl terminus of CXCR2 that is involved in adaptin 2 binding and receptor internalization. Fan, G.H., Yang, W., Wang, X.J., Qian, Q., Richmond, A. Biochemistry (2001) [Pubmed]
  29. 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]
  30. CXCR2 stimulation primes CXCR1 [Ca2+]i responses to IL-8 in human neutrophils. Hauser, C.J., Fekete, Z., Goodman, E.R., Kleinstein, E., Livingston, D.H., Deitch, E.A. Shock (1999) [Pubmed]
  31. IL-8-mediated cell migration in endothelial cells depends on cathepsin B activity and transactivation of the epidermal growth factor receptor. Schraufstatter, I.U., Trieu, K., Zhao, M., Rose, D.M., Terkeltaub, R.A., Burger, M. J. Immunol. (2003) [Pubmed]
  32. Cytokine-directed therapies for the treatment of chronic airway diseases. Barnes, P.J. Cytokine Growth Factor Rev. (2003) [Pubmed]
  33. Granulocyte chemotactic protein 2 acts via both IL-8 receptors, CXCR1 and CXCR2. Wolf, M., Delgado, M.B., Jones, S.A., Dewald, B., Clark-Lewis, I., Baggiolini, M. Eur. J. Immunol. (1998) [Pubmed]
  34. Extent and distribution of linkage disequilibrium around the SLC11A1 locus. Yip, S.P., Leung, K.H., Lin, C.K. Genes Immun. (2003) [Pubmed]
  35. Associations of classic Kaposi sarcoma with common variants in genes that modulate host immunity. Brown, E.E., Fallin, D., Ruczinski, I., Hutchinson, A., Staats, B., Vitale, F., Lauria, C., Serraino, D., Rezza, G., Mbisa, G., Whitby, D., Messina, A., Goedert, J.J., Chanock, S.J. Cancer Epidemiol. Biomarkers Prev. (2006) [Pubmed]
  36. A novel flow cytometric assay of human whole blood neutrophil and monocyte CD11b levels: upregulation by chemokines is related to receptor expression, comparison with neutrophil shape change, and effects of a chemokine receptor (CXCR2) antagonist. Nicholson, G.C., Tennant, R.C., Carpenter, D.C., Sarau, H.M., Kon, O.M., Barnes, P.J., Salmon, M., Vessey, R.S., Tal-Singer, R., Hansel, T.T. Pulmonary pharmacology & therapeutics (2007) [Pubmed]
  37. Expression and functional activity of the IL-8 receptor type CXCR1 and CXCR2 on human mast cells. Lippert, U., Artuc, M., Grützkau, A., Möller, A., Kenderessy-Szabo, A., Schadendorf, D., Norgauer, J., Hartmann, K., Schweitzer-Stenner, R., Zuberbier, T., Henz, B.M., Krüger-Krasagakes, S. J. Immunol. (1998) [Pubmed]
  38. The CXC receptor 2 is overexpressed in psoriatic epidermis. Kulke, R., Bornscheuer, E., Schlüter, C., Bartels, J., Röwert, J., Sticherling, M., Christophers, E. J. Invest. Dermatol. (1998) [Pubmed]
  39. Interleukin-8: novel roles in human airway smooth muscle cell contraction and migration. Govindaraju, V., Michoud, M.C., Al-Chalabi, M., Ferraro, P., Powell, W.S., Martin, J.G. Am. J. Physiol., Cell Physiol. (2006) [Pubmed]
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