A novel CXCL8-IP10 hybrid protein is effective in blocking pulmonary pathology in a mouse model of Klebsiella pneumoniae infection

Chen, Zhangbo; Chen, Xiangyu; Cheng, Hsi-Tsung; Yeh, Shu-Chi A.; Yu, Huiyuan; Cheng, Jya‐Wei; Li, Fang

doi:10.1016/j.intimp.2018.06.040

Cited by 5 publications

(6 citation statements)

References 35 publications

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“…CXCL8-IP10 effectively antagonizes human neutrophil responses to ELR-CXC chemokine CXCL8 21. Moreover, CXCL8-IP10 was found to efficiently block pulmonary pathology in a mouse model of Klebsiella pneumoniae infection 21…”

Section: Discussionmentioning

confidence: 97%

“…These redundantly expressed chemokines all bind to either the CXCR1 or CXCR2, and collectively recruit neutrophils into the local inflammatory responses9 in a complex multistep process 37–39. We have previously designed CXCL8-IP10, a very high-affinity antagonist of CXCR1 and CXCR2, based on the structures of CXCL8 and IP10 21. CXCL8-IP10 has a structural frame of CXCL8 and the 30’s loop of CXCL10 benefited from strong receptor-binding affinity but not the neutrophil-attracting properties 21.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously designed CXCL8-IP10, a very high-affinity antagonist of CXCR1 and CXCR2, based on the structures of CXCL8 and IP10 21. CXCL8-IP10 has a structural frame of CXCL8 and the 30’s loop of CXCL10 benefited from strong receptor-binding affinity but not the neutrophil-attracting properties 21. CXCL8-IP10 effectively antagonizes human neutrophil responses to ELR-CXC chemokine CXCL8 21.…”

Section: Discussionmentioning

confidence: 99%

“…CXCL8-IP10 has a structural frame of CXCL8 and the 30’s loop of CXCL10 benefited from strong receptor-binding affinity but not the neutrophil-attracting properties 21. CXCL8-IP10 effectively antagonizes human neutrophil responses to ELR-CXC chemokine CXCL8 21. Moreover, CXCL8-IP10 was found to efficiently block pulmonary pathology in a mouse model of Klebsiella pneumoniae infection 21…”

Section: Discussionmentioning

confidence: 99%

“…Previously, we have developed a novel ELR-CXC chemokine antagonist CXCL8-IP10 based on the structure of CXCL8 and IP10 20. We have demonstrated that CXCL8-IP10 markedly reduced Klebsiella -induced pulmonary inflammation, as assessed by gross pathology and histopathology, and airway neutrophil responses as well as airway and lung parenchymal myeloperoxidase, IL-1β, IL-6, IL-10, IFNγ, and TNF-α levels 21. Herein, we study the anticancer efficacies of the blockade of CXCL8-CXCR1/2 axis in the LL/2 model using CXCL8-IP10.…”

Section: Introductionmentioning

confidence: 99%

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<p>A novel CXCL8 analog is effective in inhibiting the growth via cell cycle arrest and attenuating invasion of Lewis lung carcinoma</p>

Hsu

Yu²,

Lee

et al. 2019

OTT

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PurposeLung cancer and other solid tumors contain not only tumor cells but various types of stromal cells, such as fibroblasts and endothelial cells. In addition, tumors are infiltrated by inflammatory cells (neutrophils, macrophages, and lymphocytes). Tumor cells, stromal cells, and the tumor-associated leukocytes are responsible for the production of chemokines inside the tumor and the maintenance of systemic circulating chemokine levels. CXCL8 and its receptors, CXCR1 and CXCR2, were found to play important roles in tumor proliferation, migration, survival, and growth. We have developed a novel ELR-CXC chemokine antagonist CXCL8-IP10 based on the structure of CXCL8 and IP10.Patients and methodsWe assessed the anticancer efficacies of the blockade of CXCL8-CXCR1/2 axis in the Lewis lung carcinoma (LL/2) model using CXCL8-IP10.ResultsWe found that CXCL8-IP10 markedly reduced LL/2 cell anchorage-independent growth and invasion. Moreover, we demonstrated that CXCL8-IP10 could significantly suppress tumor growth and improve survival rate as well as lifespan of C57BL/6 mice inoculated with LL/2 cells.ConclusionOur results suggest that ELR-CXC chemokine antagonism would potentially be a useful therapeutic approach in patients with lung cancer.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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<p>A novel CXCL8 analog is effective in inhibiting the growth via cell cycle arrest and attenuating invasion of Lewis lung carcinoma</p>

Hsu

Yu²,

Lee

et al. 2019

OTT

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CXCL8 chemokine in ulcerative colitis

Zhu

Yang²,

Zhao

et al. 2021

Biomedicine & Pharmacotherapy

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Identification of key genes and biological pathways in chronic obstructive pulmonary disease using bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2024

Preprint

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Identification of accurate biomarkers is still particularly urgent for improving the poor survival of chronic obstructive pulmonary disease (COPD) patients. In this investigation, we aimed to identity the potential biomarkers in COPD via bioinformatics and next generation sequencing (NGS) data analysis. In this investigation, the differentially expressed genes (DEGs) in COPD were identified using NGS dataset (GSE239897) from Gene Expression Omnibus (GEO) database. Subsequently, gene ontology (GO) and pathway enrichment analysis was conducted to evaluate the underlying molecular mechanisms involved in progression of COPD. Protein-protein interaction (PPI), modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network analysis were performed to determine the hub genes, miRNAs and TFs. The receiver operating characteristic (ROC) analysis was performed to determine the diagnostic value of hub genes. A total of 956 overlapping DEGs (478 up regulated and 478 down regulated genes) were identified in the NGS dataset. DEGs were mainly associated with GO functional terms and pathways in cellular response to stimulus. response to stimulus, immune system and neutrophil degranulation. There were 10 hub genes (MYC, LMNA, VCAM1, MAPK6, DDX3X, SHMT2, PHGDH, S100A9, FKBP5 and RPS6KA2) identified by PPI, modules, miRNA-hub gene regulatory network and TF-hub gene regulatory network analysis. In conclusion, the DEGs, relative GO terms, pathways and hub genes identified in the present investigation might aid in understanding of the molecular mechanisms underlying COPD progression and provide potential molecular targets and biomarkers for COPD.

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A novel CXCL8-IP10 hybrid protein is effective in blocking pulmonary pathology in a mouse model of Klebsiella pneumoniae infection

Cited by 5 publications

References 35 publications

<p>A novel CXCL8 analog is effective in inhibiting the growth via cell cycle arrest and attenuating invasion of Lewis lung carcinoma</p>

<p>A novel CXCL8 analog is effective in inhibiting the growth via cell cycle arrest and attenuating invasion of Lewis lung carcinoma</p>

CXCL8 chemokine in ulcerative colitis

Identification of key genes and biological pathways in chronic obstructive pulmonary disease using bioinformatics and next generation sequencing data analysis

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