Direct anti-inflammatory effects of granulocyte colony-stimulating factor (G-CSF) on activation and functional properties of human T cell subpopulations in vitro

Малащенко, В. В.; Meniailo, M. E.; Shmarov, V.A.; Газатова, Н. Д.; Melashchenko, Olga Borisovna; Гончаров, А. Г.; Селедцова, Г. В.; Селедцов, В. И.

doi:10.1016/j.cellimm.2018.01.007

Cited by 32 publications

(22 citation statements)

References 31 publications

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“…Additionally, ∆SH-C-85473-immunized mice showed a distinct pulmonary cytokine/chemokine profile after viral challenge, with a significant increasing expression of several HMPV-response related markers compared to the WT and ∆G-C-85473 immunized groups ( Figure 6A). Interestingly, a high expression of IL-10 cytokine [45] and G-CSF chemokine, which were reported as T-cell activators [46], was concomitant with an enhanced recruitment of immune cells (T CD4+, T CD8+, B cells) in lungs of ∆SH-C-85473-immunized mice at five days post-challenge ( Figure 6B). Moreover, such a production of anti-inflammatory cytokine/chemokine counteracts the observed increased production of TNF-α and IL-6 pro-inflammatory ( Figure 6A).…”

Section: Discussionmentioning

confidence: 88%

Strain-Dependent Impact of G and SH Deletions Provide New Insights for Live-Attenuated HMPV Vaccine Development

et al. 2019

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Human metapneumovirus (HMPV) is a major pediatric respiratory pathogen with currently no specific treatment or licensed vaccine. Different strategies to prevent this infection have been evaluated, including live-attenuated vaccines (LAV) based on SH and/or G protein deletions. This approach showed promising outcomes but has not been evaluated further using different viral strains. In that regard, we previously showed that different HMPV strains harbor distinct in vitro fusogenic and in vivo pathogenic phenotypes, possibly influencing the selection of vaccine strains. In this study, we investigated the putative contribution of the low conserved SH or G accessory proteins in such strain-dependent phenotypes and generated recombinant wild type (WT) and SH- or G-deleted viruses derived from two different patient-derived HMPV strains, A1/C-85473 and B2/CAN98-75. The ΔSH and ΔG deletions led to different strain-specific phenotypes in both LLC-MK2 cell and reconstituted human airway epithelium models. More interestingly, the ΔG-85473 and especially ΔSH-C-85473 recombinant viruses conferred significant protection against HMPV challenge and induced immunogenicity against a heterologous strain. In conclusion, our results show that the viral genetic backbone should be considered in the design of live-attenuated HMPV vaccines, and that a SH-deleted virus based on the A1/C-85473 HMPV strain could be a promising LAV candidate as it is both attenuated and protective in mice while being efficiently produced in a cell-based system.

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Section: Discussionmentioning

confidence: 88%

Strain-Dependent Impact of G and SH Deletions Provide New Insights for Live-Attenuated HMPV Vaccine Development

et al. 2019

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“…We observed a non‐significant increase in IP‐10 in the CC group compared to the WSC group ( P = 0.07), with a positive correlation between IP‐10 and RANTES, which could contribute to a pro‐inflammatory tumour environment in cancer cachectic patients. In addition, there were negative correlations between IP‐10 and GCSF, an antiapoptotic, antiangiogenic, and anti‐inflammatory factor, and between MCP‐1 and GCSF, in the peritumoural adipose tissue of the CC group patients but not the WSC group patients. It has also been found that LPS‐challenged macrophages secrete IL‐1β, IL‐6, and TNF‐α, increasing the proliferation and migration of colon cancer cells.…”

Section: Discussionmentioning

confidence: 94%

Peritumoural adipose tissue pro‐inflammatory cytokines are associated with tumoural growth factors in cancer cachexia patients

Neto

Murari

Oyama

et al. 2018

J cachexia sarcopenia muscle

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BackgroundCancer cachexia (CC) is a multifactorial syndrome, often irreversible, that affects patients with cancer influenced, in part, by the inflammatory condition. Peritumoural adipose tissue produces adipokines and angiogenic, apoptotic, and growth factors; given the possible crosstalk between the peritumoural adipose tissue and tumour, these may play an important role in cancer biology and carcinogenesis.MethodsThe aim of this study was to evaluate the factors produced by peritumoural adipose tissue in a cohort of 16 colorectal cancer patients with either weight‐stable cancer (WSC; n = 7) or CC (n = 9). The study was approved by the Ethics Research Committee (972.914). Samples of peritumoural adipose tissue were analysed for concentrations of TNF‐α, IL‐1β, STAT‐1, STAT‐3, RANTES, IL‐1Ra, IP‐10, IL‐15, MCP‐1, IFN‐α, GCSF, FADD, and TGF‐β. The cytokines and proteins were measured using Multiplex. Correlations between the proteins and cytokines were evaluated.ResultsTNF‐α, STAT‐1, and FADD, a factor involved in apoptosis, were significantly higher in CC group than in the WSC group. In the peritumoural adipose tissue of the CC group, RANTES showed a significant positive correlation with IL‐1Ra and IP‐10 and a negative correlation with IFN‐α; and GCSF showed significant negative correlations with IL‐1Ra, IP‐10, IL‐15, and MCP‐1 and a positive correlation with IFN‐α. In the peritumoural adipose tissue of the WSC group, no significant correlations were detected between RANTES, GCSF, IL‐3, FADD, and STAT‐1 and the cytokines/chemokines analysed.ConclusionsThese results indicated that inflammatory and tumorigenic pathways were altered in peritumoural adipose tissue in CC. Furthermore, inflammatory cytokines were correlated with growth factors in the peritumoural adipose tissue of cachectic patients, suggesting that inflammatory cytokines modulated the proliferative environment closely linked to the tumour.

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“…Of note, the level of granulocyte-colony stimulating factor (G-CSF) that has been reported to have an anti-inflammatory role was also significantly elevated by P12 ( Fig. 2a, b and Additional file 1: Figure S4) in the BALF and serum [30][31][32][33]. Interestingly, the M2 inducing cytokines IL-4 and IL-13 were significantly elevated in the serum (Additional file 1: Figure S4).…”

Section: The Impacts Of Peptide-coated Gnps (P12) On Global Cytokine mentioning

confidence: 93%

“…The cytokine G-CSF was reported to exhibit anti-inflammatory activity and enhance alveolar epithelial wound repair as well as facilitate clearance of apoptotic cells by macrophages in animal models [47]. Interestingly, it was found that low concentration of G-CSF could down-regulate the expression of the M1 driving cytokine IFN-γ, while high concentration of G-CSF could up-regulate the production of M2 driving cytokine IL-4 in activated T cells [32]. Indeed, the elevated IL-4 levels were observed in mouse serum (Additional file 1: Figure S4).…”

Section: Possible Mechanism(s) Of M2 Macrophage Polarization By Peptimentioning

confidence: 99%

Manipulation of macrophage polarization by peptide-coated gold nanoparticles and its protective effects on acute lung injury

et al. 2020

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Background: Macrophage polarization and reprogramming in the lung play a critical role in the initiation, development and progression of acute lung injury (ALI). Regulating the activation and differentiation of pulmonary macrophages may provide a potential therapeutic strategy to treat ALI. We previously developed a novel class of antiinflammatory nanoparticles (P12) that can potently inhibit Toll-like receptor (TLR) signaling in macrophages. These bioactive nanodevices were made of gold nanoparticles (GNPs) coated with hexapeptides to not only ensure their physiological stability but also enable GNPs with TLR inhibitory activity.Results: In this study, using a lipopolysaccharide (LPS) induced ALI mouse model, we showed that P12 was able to alleviate lung inflammation and damage through reducing the infiltration of inflammatory cells and increasing the anti-inflammatory cytokine (IL-10) in the lung. These results prompted us to investigate possible macrophage polarization by P12. We first confirmed that P12 primarily targeted macrophages in the lung to exert anti-inflammatory activity. We then showed that P12 could drive the polarization of mouse bone marrow-derived macrophages (BMDMs) toward anti-inflammatory M2 phenotype. Interestingly, in the ALI mouse model, P12 was able to increase the alveolar M2 macrophages and reduce both the alveolar and interstitial M1 macrophages in the bronchoalveolar lavage fluid (BALF) and lung tissues. Conclusion:This study demonstrated that peptide-coated GNPs could induce M2 macrophage polarization in vitro and in vivo to effectively regulate lung inflammation, protect lung from injuries and promote inflammation resolution. The ability of regulating macrophage polarization together with TLR inhibition made such a bioactive nanodevice a new generation of potent therapeutics to treat ALI.

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Direct anti-inflammatory effects of granulocyte colony-stimulating factor (G-CSF) on activation and functional properties of human T cell subpopulations in vitro

Cited by 32 publications

References 31 publications

Strain-Dependent Impact of G and SH Deletions Provide New Insights for Live-Attenuated HMPV Vaccine Development

Strain-Dependent Impact of G and SH Deletions Provide New Insights for Live-Attenuated HMPV Vaccine Development

Peritumoural adipose tissue pro‐inflammatory cytokines are associated with tumoural growth factors in cancer cachexia patients

Manipulation of macrophage polarization by peptide-coated gold nanoparticles and its protective effects on acute lung injury

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