Disease relevance of Il8rb

• Susceptibility to experimental Lyme arthritis correlates with KC and monocyte chemoattractant protein-1 production in joints and requires neutrophil recruitment via CXCR2 [1].
• In models of acute lung injury, CXC chemokine receptor 2 (CXCR2) mediates migration of polymorphonuclear leukocytes (PMNs) into the lung [2].
• Depletion of CXCR2 inhibits tumor growth and angiogenesis in a murine model of lung cancer [3].
• Moreover, we found a marked reduction in the spontaneous metastases of heterotopic tumors to the lungs of CXCR2(-/-) mice [3].
• Thus, CXCR2 may be a relevant target in the pathogenesis of RSV bronchiolitis, since it contributes to mucus production and airway hyperreactivity in our model of RSV infection [4].
• These results highlight evidences that the failure of neutrophils to migrate to an infection focus during severe sepsis is associated with excessive NO production and NO-dependent regulation of the expression of CXCR2 on the neutrophil surface [5].

High impact information on Il8rb

• We show that the functional responses of freshly isolated human and murine neutrophils to CXCR2 chemokines are significantly attenuated by SDF-1alpha, acting via CXCR4 [6].
• Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence [6].
• Neutrophil adhesion was unchanged in CXCR2(-/-), E-selectin(-/-), PTx-treated WT, or mAb 9A9-treated WT mice [7].
• Since CXCR2 ligands, including CXCL1 and CXCL2/3, are chemotactic for PMNs, CXCR2 is thought to recruit PMNs by inducing chemotactic migration [2].
• Cell culture, immunohistochemistry, flow cytometry, and real-time RT-PCR were used to show expression of CXCR2 on pulmonary endothelial and bronchial epithelial cells [2].

Chemical compound and disease context of Il8rb

• The murine homolog of the interleukin-8 receptor CXCR-2 is essential for the occurrence of neutrophilic inflammation in the air pouch model of acute urate crystal-induced gouty synovitis [8].

Biological context of Il8rb

• These data suggest that the roles for these chemokines and their receptors during development may be more significant than was initially thought based upon the phenotype of the mice with targeted deletion of CXCR2 and Duffy [9].
• Targeted deletion of the gene encoding murine CXCR2 does not result in obvious changes in the development of the organ system of the mouse, though the CXCR2-/- mouse is compromised with regard to its ability to resist infection, heal wounds, and maintain homeostasis when challenged with microbes and/or chemicals [9].
• In a model of PMN recruitment to the lung, aerosolized bacterial LPS inhalation induced PMN recruitment to the lung in wild-type mice, but not in littermate CXCR2-/- mice [2].
• The LPS-induced increase in lung microvascular permeability as measured by Evans blue extravasation required CXCR2 on nonhematopoietic cells [2].
• Growth Regulated Oncogene-alpha (GRO-alpha) is an autocrine growth factor in melanoma and is a member of the C-X-C family of chemokines which promote chemotaxis of granulocytes and endothelia through binding to CXC Receptor 2 [10].

Anatomical context of Il8rb

• In recipients of mIL-8RH+/+ marrow, mIL-8RH colocalized with densely accumulated intimal MOMA-2 positive macrophages [11].
• We now demonstrate the dependence of this process on CXC chemokine receptor 2 (CXCR2) and vascular cell adhesion molecule-1 (VCAM-1) using null strains and mice sublethally irradiated and bone marrow (BM) reconstituted (SIBR) with wild-type or null BM or with wild-type BM followed by administration of blocking antibody [12].
• Constitutive homing of mast cell progenitors to the intestine depends on autologous expression of the chemokine receptor CXCR2 [12].
• Thus, the establishment and maintenance of MCps in the small intestine is a dynamic process that requires expression of the alpha4beta7 integrin and the alpha-chemokine receptor CXCR2 [12].
• Neutrophils in CXCR2(-/-) mice were marginalized within blood vessels and could not enter the joint tissue [1].

Associations of Il8rb with chemical compounds

• Finally, the half-life of intestinal MCps in wild-type mice was less than one week on the basis of a more than 50% reduction by administration of anti-alpha4beta7 integrin or anti-CXCR2 [12].
• CXCR2 is critical to hyperoxia-induced lung injury [13].
• At days 3 and 7 after conidia, CXCR2-/- mice exhibited significantly greater methacholine-induced airway hyperreactivity than did CXCR2+/+ mice [14].
• Furthermore, there was no difference in liver injury between BALB/cJ wild-type and CXC receptor-2 gene knockout (CXCR2-/-) mice treated with Gal/ET [15].
• The delayed addition of ELR-CXC chemokines to cultured hepatocytes maintained the proliferation of these cells in a CXCR2-dependent fashion after acetaminophen challenge whereas delayed NAC treatment did not [16].

Regulatory relationships of Il8rb

• Together, these results show that a CXC chemokine such as GRO-alpha can promote malignant growth of murine squamous cell carcinoma by a host CXCR-2 dependent pathway [10].
• Furthermore, IP-10 treatment of cultured hepatocytes stimulated a CXCR2-dependent proliferative response [17].
• A synthetic, non-peptide CXCR2 antagonist blocks MIP-2-induced neutrophil migration in mice [18].
• As an underlying mechanism, KC was involved in promoting CXCR2-mediated endothelial chemotaxis and wound repair [19].

Other interactions of Il8rb

• Thus, the capacity of leukocytes to express mIL-8RH, and associated intralesional expression of its ligands such as KC/GROalpha, mediated the intimal accumulation of macrophages in atherosclerotic lesions of LDL receptor-deficient mice [11].
• Antibody blockade of VCAM-1 or of CXCR2 in SIBR mice reduced intestinal MCp reconstitution, and mice lacking endothelial VCAM-1 also had a marked reduction relative to wild-type mice [12].
• Infection of CXCR2(-/-) mice on either genetic background resulted in a significant decrease in the development of pathology, although infection of CCR2(-/-) mice had little or no effect [1].
• We observed strong correlation between the expression of MIP-2 and CXCR2 in the developing brain, cardiovascular system and condensing mesenchyme between 11.5 and 13.5 days [9].
• The selective blockade of CXCR2 or CCR1 inhibited neutrophil recruitment by 74% and 54%, respectively, without a significant inhibition of monocytes [20].

Analytical, diagnostic and therapeutic context of Il8rb

• 2. In the first week, mast cell degranulation and leukocyte influx (mononuclear cell, MNC, and polymorphonuclear cell, PMN) were associated with CXCR2, KC and macrophage inflammatory protein (MIP)-2 mRNA expression, as determined by TaqMan reverse transcriptase-polymerase chain reaction [21].
• Surprisingly, lethally irradiated wild-type mice reconstituted with CXCR2-/- BM still showed about 50% PMN recruitment into bronchoalveolar lavage fluid and into lung interstitium, but CXCR2-/- mice reconstituted with CXCR2-/- BM showed no PMN recruitment [2].
• In contrast, CXCR2-deficient mice exhibited significantly less airway hyperresponsiveness than the wild-type control groups at days 14 and 37 after conidia [14].
• To isolate the role of CXCR2 specifically on blood cells, adoptive transfer experiments were performed [22].
• Compared with allografts retrieved from control recipients, both PMN infiltration and intragraft proinflammatory cytokine expression were significantly attenuated in allografts from CXCR2-antisera-treated wild-type or from CXCR2(-/-) recipients [23].

References