Cloning of a cDNA encoding a mouse homolog of the interleukin-8 receptor

Harada, Akihisa; Kuno, Kouji; Nomura, Hideki; Mukaida, Naofumi; Murakami, Seishi; Matsushima, Kouji

doi:10.1016/0378-1119(94)90278-x

Cited by 37 publications

(18 citation statements)

References 12 publications

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“…Previous studies report that, in the progression of certain solid tumors, CXCL8-mediated activation of the CXCR2 biological axis is important for the regulation of the phosphoinositide 3 kinase/Ras/Raf pathway (30)(31)(32). The differences between CXCR1 and CXCR2 were previously identified, and the latter showed a high affinity for binding to numerous ligands, including CXCL8, CXCL1, CXCL2, CXCL5 and GCP-2 (13)(14)(15)30,31,(33)(34)(35).…”

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confidence: 99%

Association between CXCR2 and IL-22BP expression indicate a poor outcome for gastric adenocarcinoma progression

Yang

Han

et al. 2016

Oncology Letters

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Abstract. C-X-C motif chemokine receptor type 2 (CXCR2), a key regulatory protein, has been associated with multiple roles in the progression of numerous tumors, including gastric adenocarcinoma (GA). However, the mechanism of CXCR2 in the development of tumors remains controversial and unclear. In a previous study, the expression of CXCR2 and interleukin-22 receptor 2 (IL-22BP) was observed in GA. This promoted the present study, which aimed to explore the association between the two proteins, and to further analyze their roles in GA. CXCR2 and IL-22BP protein expression was analyzed by immunohistochemistry and reverse transcription-quantitative polymerase chain reaction assays in gastric cancer (GC) tissue, additionally confirmed via western blotting and immunocytochemical analysis in the MKN-45, BGC-823 and SGC-7901 cell lines. The association between expression levels and clinicopathological characteristics was evaluated by the Mann-Whitney U and Kruskal-Wallis tests. Using Kaplan-Meier plots and Cox proportional hazard models, overall survival (OS) was analyzed. Compared with non-cancerous tissue, CXCR2 and IL-22BP were over expressed (P<0.001 and P<0.001, respectively), and were observed mainly in the cytoplasm (P=0.022 and P=0.014, respectively) in GA. The associated protein and messenger RNA levels were analyzed, and coexpression was identified. Increased expression and more positive cases of CXCR2 and IL-22BP were observed with advanced pathological tumor-node-metastasis (p-TNM) stage in GC (P<0.001 and P<0.001, respectively), as well as the presence and absence of lymph node metastasis (LNM) (P=0.003 and P=0.041, respectively) and deep or superficial muscular invasion (P=0.002 and P=0.004, respectively). In addition, an association between IL-22BP and tumor diameter was indicated (P=0.021). In a Kaplan-Meier analysis, compared with negative expression, the two proteins identified a group of patients with the shortest OS. Cox proportional hazard models revealed that the two proteins, in addition to p-TNM stage, LNM and depth of invasion, predicted a short time to OS. The coexpression of CXCR2 and IL-22BP was demonstrated in GA, which may indicate that CXCR2 is involved in more complex mechanisms and roles, and indicate a poor outcome in GA progression.

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confidence: 99%

Association between CXCR2 and IL-22BP expression indicate a poor outcome for gastric adenocarcinoma progression

Yang

Han

et al. 2016

Oncology Letters

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“…Macrophages are reported to be the main sources for MIP-2 and KC, whereas LIX and lungkine are predominantly produced by fibroblasts and lung epithelial cells, respectively (21,36,38,46). Two receptors for ELR ϩ CXC chemokines, CXC chemokine receptors 1 and 2 (CXCR1 and CXCR2, respectively), have been identified for humans (24); mice have only CXCR2 which, like its human counterpart, binds all ELR ϩ CXC chemokines (5,17,23). In CXCR2 knockout mice, neutrophils were not recruited in vivo in response to MIP-2 or KC but did respond to other chemoattractants, suggesting that the binding of ELR ϩ CXC chemokines to CXCR2 is essentially for neutrophil recruitment and that CXCR2 is the exclusive receptor for these ligands (23).…”

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Chemokine-Dependent Neutrophil Recruitment in a Murine Model ofLegionellaPneumonia: Potential Role of Neutrophils as Immunoregulatory Cells

et al. 2001

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The roles of CXC chemokine-mediated host responses were examined with an A/J mouse model of Legionella pneumophila pneumonia. After intratracheal inoculation of 10 6 CFU of L. pneumophila, the bacterial numbers in the lungs increased 10-fold by day 2; this increase was accompanied by the massive accumulation of neutrophils. Reverse transcription-PCR data demonstrated the up-regulation of CXC chemokines, such as keratinocyte-derived chemokine, macrophage inflammatory protein 2 (MIP-2), and lipopolysaccharide-induced CXC chemokine (LIX). Consistent with these data, increased levels of KC, MIP-2, and LIX proteins were observed in the lungs and peaked at days 1, 2, and 2, respectively. Although the administration of anti-KC or anti-MIP-2 antibody resulted in an approximately 20% decrease in neutrophil recruitment on day 2, no increase in mortality was observed. In contrast, the blockade of CXC chemokine receptor 2 (CXCR2), a receptor for CXC chemokines, including KC and MIP-2, strikingly enhanced mortality; this effect coincided with a 67% decrease in neutrophil recruitment. Interestingly, anti-CXCR2 antibody did not affect bacterial burden by day 2, even in the presence of a lethal challenge of bacteria. Moreover, a significant decrease in interleukin-12 (IL-12) levels, in contrast to the increases in KC, MIP-2, and LIX levels, was demonstrated for CXCR2-blocked mice. These data indicated that CXCR2-mediated neutrophil accumulation may play a crucial role in host defense against L. pneumophila pneumonia in mice. The increase in lethality without a change in early bacterial clearance suggested that neutrophils may exert their protective effect not through direct killing but through more immunomodulatory actions in L. pneumophila pneumonia. We speculate that a decrease in the levels of the protective cytokine IL-12 may explain, at least in part, the high mortality in the setting of reduced neutrophil recruitment.

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“…C-C chemokine receptors are approximately 45-60% identical to each other, while the two functional C-X-C (IL-8) receptors are 78% identical to one another. Genes encoding chemokine receptors have also been identified in the mouse (15)(16)(17)(18)(19)(20)(21)(22). Despite the apparent absence of a rodent ortholog of the human IL-8 peptide, a single murine ortholog of the human IL-8 receptors has been cloned (15)(16)(17).…”

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confidence: 99%

“…Genes encoding chemokine receptors have also been identified in the mouse (15)(16)(17)(18)(19)(20)(21)(22). Despite the apparent absence of a rodent ortholog of the human IL-8 peptide, a single murine ortholog of the human IL-8 receptors has been cloned (15)(16)(17). This receptor binds the rodent C-X-C chemokines, macrophage inflammatory peptide-2 (MIP-2), and KC/CINC (cytokine induced neutrophil chemoattractant) as well as human IL-8 and GRO-␣.…”

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confidence: 99%

Identification of Two Rat Genes Orthologous to the Human Interleukin-8 Receptors

Dunstan

Salafranca

Adhikari

et al. 1996

Journal of Biological Chemistry

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The genes encoding two functional human interleukin-8 (IL-8) receptors have been identified by molecular cloning techniques and they are members of the rhodopsin G-protein coupled receptor (GCR) superfamily. We report the molecular cloning of two rat GCR genes (rat CXCR1-like and rat CXCR2) whose conceptualized amino acid sequences are approximately 70% identical to the human IL-8 A and B receptor subtypes. The murine GRO-like peptide, macrophage inflammatory peptide-2 (MIP-2), elevates intracellular calcium levels in HEK293 cells expressing the rat CXCR2 receptor. Southern blot analysis of restriction-digested rodent and human genomic DNAs indicate that rat CXCR1-like and CXCR2 are: 1) each single copy genes in the rat genome; 2) most closely related to the human IL-8 receptor genes; and 3) orthologous to two previously identified murine genes. CXCR2 mRNA is detected in adult rat lung, spleen, and neutrophils. CXCR1-like mRNA can be detected in adult rat lung, native rat macrophages, and a rat alveolar macrophage cell line (NR8383). These data identify the rat orthologs of the human IL-8 receptors, and describe cellular and tissue targets of rat C-X-C chemokine peptides.

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Cloning of a cDNA encoding a mouse homolog of the interleukin-8 receptor

Cited by 37 publications

References 12 publications

Association between CXCR2 and IL-22BP expression indicate a poor outcome for gastric adenocarcinoma progression

Association between CXCR2 and IL-22BP expression indicate a poor outcome for gastric adenocarcinoma progression

Chemokine-Dependent Neutrophil Recruitment in a Murine Model ofLegionellaPneumonia: Potential Role of Neutrophils as Immunoregulatory Cells

Identification of Two Rat Genes Orthologous to the Human Interleukin-8 Receptors

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