Combined anti CXC receptors 1 and 2 therapy is a promising anti-inflammatory treatment for respiratory diseases by reducing neutrophil migration and activation

Planagumà, Anna; Domènech, Teresa; Pont, Mercè; Calama, Elena; García-González, Vicente; López, Rosa; Aulí, Mariona; Lopez, Michel Angel; Fonquerna, Sı́lvia; Ramos, Israel; Alba, Jorge De; Nueda, Arsenio; Prats, Neus; Segarra, Vı́ctor; Miralpeix, Montserrat; Lehner, Martin D.

doi:10.1016/j.pupt.2015.08.002

Cited by 44 publications

(30 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CXCL1 is a potent proinflammatory mediator of inflammatory diseases and infection, and is widely considered to both promote and exacerbate tumor growth and progression in several cancers [25,26]. CXCL1 is upregulated in various cancers and associated with cancer progression, such as cancer cell growth, proliferation, tumor angiogenesis and metastasis, after the activation of CXCR2 [27,28,29].…”

Section: Discussionmentioning

confidence: 99%

Interaction between Tumor-Associated Dendritic Cells and Colon Cancer Cells Contributes to Tumor Progression via CXCL1

Hsu

Chen

Chang

et al. 2018

IJMS

View full text Add to dashboard Cite

Crosstalk of a tumor with its microenvironment is a critical factor contributing to cancer development. This study investigates the soluble factors released by tumor-associated dendritic cells (TADCs) responsible for increasing cancer stem cell (CSC) properties, cell mobility, and epithelial-to-mesenchymal transition (EMT). Dendritic cells (DCs) of colon cancer patients were collected for phenotype and CXCL1 expression by flow cytometry and Luminex assays. The transcriptome of CXCL1-treated cancer cells was established by next generation sequencing. Inflammatory chemokine CXCL1, present in large amounts in DCs isolated from colon cancer patients, and SW620-conditioned TADCs, enhance CSC characteristics in cancer, supported by enhanced anchorage-independent growth, CD133 expression and aldehyde dehydrogenase activity. Additionally, CXCL1 increases the metastatic ability of a cancer by enhancing cell migration, matrix metalloproteinase-7 expression and EMT. The enhanced CXCL1 expression in DCs is also noted in mice transplanted with colon cancer cells. Transcriptome analysis of CXCL1-treated SW620 cells indicates that CXCL1 increases potential oncogene expression in colon cancer, including PTHLH, TYRP1, FOXO1, TCF4 and ZNF880. Concurrently, CXCL1 displays a specific microRNA (miR) upregulated by the prototypical colon cancer onco-miR miR-105. Analysis of publicly available data reveals CXCL1-driven oncogenes and miR-105 have a negative prognostic impact on the outcome of colon cancer. This study indicates a new mechanism by which the colon cancer milieu exploits DC plasticity to support cancer progression.

show abstract

Section: Discussionmentioning

confidence: 99%

Interaction between Tumor-Associated Dendritic Cells and Colon Cancer Cells Contributes to Tumor Progression via CXCL1

Hsu

Chen

Chang

et al. 2018

IJMS

View full text Add to dashboard Cite

show abstract

“…It is also intriguing that Cxcr2 mediates neutrophil recruitment to infection but not sterile inflammation, suggesting the involvement of additional cues that act in combination to influence neutrophil migration. There has been substantial interest in developing small molecules that block Cxcr1/Cxcr2 signaling to limit inflammation and treat human disease (Busch-Petersen, 2006; Jamieson et al, 2012; Khan et al, 2015; Planaguma et al, 2015). Some of these compounds are in clinical trials to treat inflammatory disease and cancer (de Oliveira et al, 2016; Stadtmann and Zarbock, 2012).…”

Section: Discussionmentioning

confidence: 99%

Chemokine Signaling and the Regulation of Bidirectional Leukocyte Migration in Interstitial Tissues

et al. 2017

View full text Add to dashboard Cite

Summary Motile cells navigate through complex tissue environments that include both attractive and repulsive cues. In response to tissue wounding, neutrophils, primary cells of the innate immune response, exhibit bidirectional migration that is orchestrated by chemokines and their receptors. Although progress has been made in identifying signals that mediate the recruitment phase, the mechanisms that regulate neutrophil reverse migration remain largely unknown. Here, we visualize bidirectional neutrophil migration to sterile wounds in zebrafish larvae and identify specific roles for the chemokine receptors Cxcr1 and Cxcr2 in neutrophil recruitment to sterile injury and infection. Notably, we also identify Cxcl8a/Cxcr2 as a specific ligand-receptor pair that orchestrates neutrophil chemokinesis in interstitial tissues during neutrophil reverse migration and resolution of inflammation. Taken together, our findings identify distinct receptors that mediate bidirectional leukocyte motility during interstitial migration depending on the context and type of tissue damage in vivo.

show abstract

“…Uncontrolled NE activity, as found in CF airways, causes further respiratory tissue damage through degradation of extracellular proteins (such as surfactant proteins [71][72][73]) and cellular surface receptors (such as complement receptors [74]); high NE levels correlating with disease severity and poorer lung function are described in both CF and non-CF bronchiectasis settings [75,76]. In this context, CXCR receptor antagonists are hypothesized to inhibit neutrophil airway influx and have been shown to be effective in modulating the inflammatory state in bronchiectasis [77,78]. Airway neutrophils in CF illustrate an impaired phagocytic ability [79].…”

Section: Immunology and Inflammationmentioning

confidence: 99%

Pathogenesis, imaging and clinical characteristics of CF and non-CF bronchiectasis

Schäfer

Griese²,

Chandrasekaran

et al. 2018

BMC Pulm Med

View full text Add to dashboard Cite

Bronchiectasis is a common feature of severe inherited and acquired pulmonary disease conditions. Among inherited diseases, cystic fibrosis (CF) is the major disorder associated with bronchiectasis, while acquired conditions frequently featuring bronchiectasis include post-infective bronchiectasis and chronic obstructive pulmonary disease (COPD). Mechanistically, bronchiectasis is driven by a complex interplay of inflammation and infection with neutrophilic inflammation playing a predominant role. The clinical characterization and management of bronchiectasis should involve a precise diagnostic workup, tailored therapeutic strategies and pulmonary imaging that has become an essential tool for the diagnosis and follow-up of bronchiectasis. Prospective future studies are required to optimize the diagnostic and therapeutic management of bronchiectasis, particularly in heterogeneous non-CF bronchiectasis populations.

show abstract

Combined anti CXC receptors 1 and 2 therapy is a promising anti-inflammatory treatment for respiratory diseases by reducing neutrophil migration and activation

Cited by 44 publications

References 28 publications

Interaction between Tumor-Associated Dendritic Cells and Colon Cancer Cells Contributes to Tumor Progression via CXCL1

Interaction between Tumor-Associated Dendritic Cells and Colon Cancer Cells Contributes to Tumor Progression via CXCL1

Chemokine Signaling and the Regulation of Bidirectional Leukocyte Migration in Interstitial Tissues

Pathogenesis, imaging and clinical characteristics of CF and non-CF bronchiectasis

Contact Info

Product

Resources

About