Disease relevance of IL8RB

• Variants of the IL8 and IL8RB genes and risk for gastric cardia adenocarcinoma and esophageal squamous cell carcinoma [1].
• By the use of pertussis toxin (PTx), it was demonstrated that the actual events of G(alphai)-coupling to CXCR2 do not have a major role in the regulation of its internalization [2].
• IL-8 and its CXCR1 and CXCR2 receptors participate in the control of megakaryocytic proliferation, differentiation, and ploidy in myeloid metaplasia with myelofibrosis [3].
• We studied model SK-OV-3 ovarian cancer cells and observed robust expression of the alpha chemokine receptors CXCR-1 and CXCR-2 [4].
• We have applied immunohistology and in situ hybridization to bronchial biopsies of patients with chronic obstructive pulmonary disease (COPD) to examine neutrophil recruitment and to determine neutrophil chemoattractant and CXC receptor (CXCR) 1 and CXCR2 gene expression associated with acute severe exacerbations [5].
• Knockdown of CXCR2 expression by small hairpin RNA reduced tumorigenesis of ovarian cancer cells in nude mice [6].

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

• Signaling through CXCR2, CXCL1 inhibited oligodendrocyte precursor migration [8].
• Here we demonstrate a role for the chemokine CXCL1 and its receptor CXCR2 in patterning the developing spinal cord [8].
• We now report cloning of the genes for IL8RA, IL8RB and a recently inactivated pseudogene of receptor A (IL8RAP) [9].
• PGP caused chemotaxis and production of superoxide through CXC receptors, and administration of peptide caused recruitment of neutrophils (PMNs) into lungs of control, but not CXCR2-deficient mice [10].
• In situ hybridization and immunohistochemistry localized DARC expression on normal brain and tumor microvascular cells and CXCR1 and CXCR2 expression to infiltrating leukocytes [11].

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

• IL8, IL8RA, and IL8RB SNPs were analyzed using a multiplex assay system, haplotypes were constructed, and risks were estimated using Cox proportional hazards models [1].
• 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 [17].
• Ca(2+) mobilization by S3 and DeltaCCR1 were also cross-desensitized by CXCR1 and CXCR2 despite lack of receptor phosphorylation [18].
• Ligand-independent CXCR2 dimerization [19].
• It is an antagonist of 125I-IL-8 binding to CXCR2 with an IC50 = 22 nM [20].

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

• Expression of mRNA for both types of IL-8 receptors (CXCR1 and CXCR2) was demonstrated by PCR and of both proteins by flow cytometry [37].
• CXCR1 and CXCR2 expression on HIMEC were defined using reverse transcriptase-PCR, immunohistochemistry, flow cytometry, and Western blot analysis [23].
• Using postembedding immunoelectron microscopy, we could show the expression of CXCRI on the cytoplasmatic membrane of isolated human skin mast cells whereas CXCR2 was located in mast cell-specific granules [37].
• By immunohistochemistry and in situ hybridization, as confirmed by northern blot analysis and reverse transcriptase polymerase chain reaction, we could detect expression of the CXCR2 in suprabasal lesional psoriatic keratinocytes but not in healthy skin [38].
• Real-time PCR and fluorescence-activated cell sorting analysis showed that HASMC expressed mRNA and protein for both CXCR1 and CXCR2 [39].

References