Anti‐inflammatory effects of the <scp>GAG</scp>‐binding <scp>CXCL</scp>9(74‐103) peptide in dinitrofluorobenzene‐induced contact hypersensitivity in mice

Vanheule, Vincent; Crijns, Helena; Poosti, Fariba; Ruytinx, Pieter; Berghmans, Nele; Gerlza, Tanja; Ronsse, Isabelle; Pörtner, Noëmie; Matthys, Patrick; Kungl, Andreas J.; Opdenakker, Ghislain; Struyf, Sofie; Proost, Paul

doi:10.1111/cea.13227

Cited by 10 publications

(15 citation statements)

References 65 publications

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“…The cross talk in chemokines and G protein-coupled receptors could lead to the migration of leukocytes during normal immune function. In tissue injury or infection, this interaction is a key component of the inflammatory response [12, 13]. Current studies showed that several chemokines, such as MCP-1, fractalkine, and SDF-1, have been linked to chronic and neuropathic pain and as the key inflammatory mediators in both human conditions and animal models [14–16].…”

Section: Discussionmentioning

confidence: 99%

Investigation of Key Genes and Pathways in Inhibition of Oxycodone on Vincristine-Induced Microglia Activation by Using Bioinformatics Analysis

Liu

Yan

2019

Disease Markers

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Introduction. The neurobiological mechanisms underlying the chemotherapy-induced neuropathic pain are only partially understood. Among them, microglia activation was identified as the key component of neuropathic pain. The aim of this study was to identify differentially expressed genes (DEGs) and pathways associated with vincristine-induced neuropathic pain by using bioinformatics analysis and observe the effects of oxycodone on these DEG expressions in a vincristine-induced microglia activation model. Methods. Based on microarray profile GSE53897, we identified DEGs between vincristine-induced neuropathic pain rats and the control group. Using the ToppGene database, the prioritization DEGs were screened and performed by gene ontology (GO) and signaling pathway enrichment. A protein-protein interaction (PPI) network was used to explore the relationship among DEGs. Then, we built the vincristine-induced microglia activation model and detected several DEG expressions by real-time polymerase chain reaction (PCR) and western blotting. Meanwhile, the effects of different concentrations of oxycodone on inflammatory response in primary microglia induced by vincristine were observed. Results. A total of 38 genes were differentially expressed between normal and vincristine-treated rats. GO and pathway enrichment analysis showed that prioritization DEGs are involved in cAMP metabolic process, inflammatory response, regulation of cell proliferation, and chemokine pathway. The in vitro studies showed that vincristine had dose-dependent cytotoxic effects in microglia. Compared to the control group, vincristine (0.001 μg/ml) could lead to inflammation in primary microglia induced by vincristine and upregulated the CXCL10, CXCL9, SFRP2, and PF4 mRNA and made an obvious reduction in IRF7 mRNA. At protein levels, oxycodone (50, 100 ng/ml) decreased the expression of CXCL10 and CXCL9 in activated microglia. Conclusion. Our study obtained several DEG expressions and signaling pathways in the vincristine-induced neuropathic pain rat model by bioinformatics analysis. Oxycodone could alleviate the vincristine-induced inflammatory signaling in primary microglia and downregulate some DEGs. Further molecular mechanisms need to be explored in the future.

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Section: Discussionmentioning

confidence: 99%

Investigation of Key Genes and Pathways in Inhibition of Oxycodone on Vincristine-Induced Microglia Activation by Using Bioinformatics Analysis

Liu

Yan

2019

Disease Markers

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“…In a murine model of antigen-induced arthritis the peptide reduced the recruitment of leukocytes, especially neutrophils, to the synovial cavity and prevented articular and cartilage damage. Moreover, CXCL9(74-103) reduced neutrophil infiltration and neutrophil-dependent inflammation in the ears of the mice in a murine contact hypersensitivity model (265).…”

Section: Chemokine-derived Gag-binding Peptidesmentioning

confidence: 96%

Targeting Chemokine—Glycosaminoglycan Interactions to Inhibit Inflammation

2020

Self Cite

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Leukocyte migration into tissues depends on the activity of chemokines that form concentration gradients to guide leukocytes to a specific site. Interaction of chemokines with their specific G protein-coupled receptors (GPCRs) on leukocytes induces leukocyte adhesion to the endothelial cells, followed by extravasation of the leukocytes and subsequent directed migration along the chemotactic gradient. Interaction of chemokines with glycosaminoglycans (GAGs) is crucial for extravasation in vivo. Chemokines need to interact with GAGs on endothelial cells and in the extracellular matrix in tissues in order to be presented on the endothelium of blood vessels and to create a concentration gradient. Local chemokine retention establishes a chemokine gradient and prevents diffusion and degradation. During the last two decades, research aiming at reducing chemokine activity mainly focused on the identification of inhibitors of the interaction between chemokines and their cognate GPCRs. This approach only resulted in limited success. However, an alternative strategy, targeting chemokine-GAG interactions, may be a promising approach to inhibit chemokine activity and inflammation. On this line, proteins derived from viruses and parasites that bind chemokines or GAGs may have the potential to interfere with chemokine-GAG interactions. Alternatively, chemokine mimetics, including truncated chemokines and mutant chemokines, can compete with chemokines for binding to GAGs. Such truncated or mutated chemokines are characterized by a strong binding affinity for GAGs and abrogated binding to their chemokine receptors. Finally, Spiegelmers that mask the GAG-binding site on chemokines, thereby preventing chemokine-GAG interactions, were developed. In this review, the importance of GAGs for chemokine activity in vivo and strategies that could be employed to target chemokine-GAG interactions will be discussed in the context of inflammation.

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“…65 In a follow-up study, Vanheule and colleagues examined whether the chemokine-GAG antagonist CXCL974-103 inhibited inflammation and neutrophildependent DFNB-induced contact hypersensitivity. 66…”

Section: Immune-targeted Approaches For the Suppression Of The Allementioning

confidence: 99%

“…Recent studies have demonstrated that CXCL974‐103 the COOH terminal peptide of human CXCL9 binds with high affinity to GAGs and inhibits CXCL8‐ and monosodium urate crystal (MSU)–induced neutrophil migration . In a follow‐up study, Vanheule and colleagues examined whether the chemokine‐GAG antagonist CXCL974‐103 inhibited inflammation and neutrophil‐dependent DFNB‐induced contact hypersensitivity . The authors demonstrated that simultaneous treatment of mice with CXCL974‐103 and DNFB inhibited clinical symptoms of CHS, ear swelling and that this was associated with a reduction in neutrophil infiltration and the level of the neutrophil‐derived proteolytic enzyme metalloproteinases MMP9.…”

Section: Experimental Models Of Allergic Diseasementioning

confidence: 99%

Developments in the mechanisms of allergy in 2018 through the eyes of Clinical and Experimental Allergy, Part I

Roberts

Almqvist

Boyle

et al. 2019

Clin Experimental Allergy

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Anti‐inflammatory effects of the GAG‐binding CXCL9(74‐103) peptide in dinitrofluorobenzene‐induced contact hypersensitivity in mice

Cited by 10 publications

References 65 publications

Investigation of Key Genes and Pathways in Inhibition of Oxycodone on Vincristine-Induced Microglia Activation by Using Bioinformatics Analysis

Investigation of Key Genes and Pathways in Inhibition of Oxycodone on Vincristine-Induced Microglia Activation by Using Bioinformatics Analysis

Targeting Chemokine—Glycosaminoglycan Interactions to Inhibit Inflammation

Developments in the mechanisms of allergy in 2018 through the eyes of Clinical and Experimental Allergy, Part I

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