Caspofungin suppresses zymosan-induced cytokine and chemokine release in THP-1 cells: possible involvement of the spleen tyrosine kinase pathway

Itoh, Kazuhiro; Shigemi, Hiroko; Chihara, Kazuyasu; Sada, Kiyonao; Yamauchi, Takahiro; Iwasaki, Hiromichi

doi:10.1016/j.trsl.2020.07.005

Cited by 14 publications

(15 citation statements)

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“…Gliomas are highly infiltrated by bone marrow-derived macrophages and brain-resident microglia, which promote tumor growth and suppress the immune response (Hambardzumyan et al, 2016). The abnormal expression of SYK in tumor cells or leukocytes may activate several signaling pathways to promote the release of some chemokines (Kodar et al, 2017;Itoh et al, 2021). We also found that tumors with high SYK expression were enriched in NF-kappaB signaling (Figure 4F).…”

Section: Discussionmentioning

confidence: 75%

SYK Is Associated With Malignant Phenotype and Immune Checkpoints in Diffuse Glioma

et al. 2022

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Background: Diffuse glioma, the most common intracranial malignant tumor, is characterized by immunosuppression. The prognostic significance and potential therapeutic value of SYK remain obscure. Here, we explored the performance of SYK in predicting patient outcomes and as a therapeutic target.Methods: The mRNA expression and clinical data for pancancer and normal tissues and more than 2,000 glioma samples were collected from public databases. The expression level of SYK was evaluated by qPCR and IHC. The prognostic value of SYK was assessed using the Kaplan–Meier curves and univariate and multivariate Cox regression analyses. A sequence of immune and stromal infiltration analyses was calculated based on the ESTIMATE algorithm, ssGSEA algorithm, TIMER, and single-cell analysis. The SYK-related subtypes were identified via a Consensus Cluster Plus analysis.Results: SYK was significantly differentially expressed in multiple tumors and normal tissues. Importantly, high-expression SYK was enriched in malignant phenotypes of diffuse gliomas, which was further validated by qPCR and IHC. Survival analysis uncovered that SYK was an independently unfavorable prognostic marker in diffuse glioma. Functional enrichment analysis and immune and stromal infiltration analyses showed that SYK was involved in shaping the immunosuppressive microenvironment of diffuse glioma. Additionally, SYK expression was closely associated with some immune checkpoint molecules and M2 macrophage infiltration, which was validated by IHC and single-cell analysis. Diffuse glioma with Sub1 exhibited a worse prognosis, immunosuppressive microenvironment, and higher expression of immune checkpoint genes.Conclusion: SYK is involved in shaping the immunosuppressive microenvironment and served as a promising prognosis biomarker and immunotherapeutic target for diffuse glioma.

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Section: Discussionmentioning

confidence: 75%

SYK Is Associated With Malignant Phenotype and Immune Checkpoints in Diffuse Glioma

et al. 2022

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“… 15 , 111 − 114 Itoh et al (2021) reported that antimicrobial compounds like TC modulate the immune cells (THP-1), while Liu et al (2019) confirmed the cytotoxicity of TC present in soil samples against human cell lines (HL-7702). 15 , 115 …”

Section: Resultsmentioning

confidence: 99%

“…The toxicity percentage of TC and its degraded products showed a negative correlation [RAW 264.7: R 2 (−0.932), p -value (0.01) and THP-1: R 2 (−0.931), p -value (0.01)] with the degradation rate, and it confirmed the degradation of the antibiotic and loss of its activity (Figure B(i,ii)). Most of the researchers used fish and other cell lines for testing of toxicity of antimicrobials, and they observed various adverse genetic mutations and cytotoxic, genotoxic, and transgenerational effects on the developing cells. − For its high toxicity and mutation and modulation effects, TC is nowadays used for the study of different tumor cell lines including mammalian cell lines (hepatic, monocytes, macrophages). ,− Itoh et al (2021) reported that antimicrobial compounds like TC modulate the immune cells (THP-1), while Liu et al (2019) confirmed the cytotoxicity of TC present in soil samples against human cell lines (HL-7702). , …”

Section: Resultsmentioning

confidence: 99%

“…105−110 For its high toxicity and mutation and modulation effects, TC is nowadays used for the study of different tumor cell lines including mammalian cell lines (hepatic, monocytes, macrophages). 15,111−114 Itoh et al (2021) reported that antimicrobial compounds like TC modulate the immune cells (THP-1), while Liu et al (2019) confirmed the cytotoxicity of TC present in soil samples against human cell lines (HL-7702). 15,115…”

Section: Effect Of Phmentioning

confidence: 99%

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Visible-Light-Driven Photocatalytic Degradation of Tetracycline Using Heterostructured Cu₂O–TiO₂Nanotubes, Kinetics, and Toxicity Evaluation of Degraded Products on Cell Lines

et al. 2022

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This study first reports on the tetracycline photodegradation with the synthesized heterostructured titanium oxide nanotubes coupled with cuprous oxide photocatalyst. The large surface area and more active sites on TiO 2 nanotubes with a reduced band gap (coupling of Cu 2 O) provide faster photodegradation of tetracycline under visible light conditions. Cytotoxicity experiments performed on the RAW 264.7 (mouse macrophage) and THP-1 (human monocytes) cell lines of tetracycline and the photodegraded products of tetracycline as well as quenching experiments were also performed. The effects of different parameters like pH, photocatalyst loading concentration, cuprous oxide concentration, and tetracycline load on the photodegradation rate were investigated. With an enhanced surface area of nanotubes and a reduced band gap of 2.58 eV, 1.5 g/L concentration of 10% C-TAC showed the highest efficiency of visible-light-driven photodegradation (∼100% photodegradation rate in 60 min) of tetracycline at pH 5, 7, and 9. The photodegradation efficiency is not depleted up to five consecutive batch cycles. Quenching experiments confirmed that superoxide radicals and hydroxyl radicals are the most involved reactive species in the photodegradation of tetracycline, while valance band electrons are the least involved reactive species. The cytotoxicity percentage of tetracycline and its degraded products on RAW 264.7 (−0.932) as well as THP-1 (-0.931) showed a negative correlation with the degradation percentage with a p -value of 0.01. The toxicity-free effluent of photodegradation suggests the application of the synthesized photocatalyst in wastewater treatment.

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“…Caspofungin is a long-standing antifungal agent [8]. Recently, Itoh K et al have demonstrated that caspofungin is able to suppress zymosan-induced cytokine and chemokine release in THP-1 cells [21], revealing the additional pharmacological action of caspofungin besides its antifungal activity. Based on this report as well as the potential interaction between caspofungin and Pellino3, we hypothesize that caspofungin may have bene cial effect on ischemic stroke.…”

Section: Discussionmentioning

confidence: 99%

Caspofungin suppresses brain cell necroptosis in the ischemic stroke rat via up-regulation of Pellino3

Zhang

Tian

Peng

et al. 2021

Preprint

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Purpose Pellino3, an ubiquitin E3 ligase, prevents the formation of the death-induced signaling complex in response to TNF-α via targeting receptor-interacting protein kinase 1 (RIPK1), and bioinformatics analysis predicts the interaction between Pellino3 and caspofungin, a common antifungal drug used in clinic. This study aims to explore the effect of caspofungin on brain injury in ischemic stroke and the underlying mechanisms. Methods The SD rat brains (or nerve cells) were subjected to 2h-ischemia (or 8h-hypoxia) plus 24h-reperfusion (or 24h-reoxygenation) to establish the I/R (or H/R) injury model. The cerebral injury was assessed by the methods of triphenyltetrazolium chloride (TTC) staining and Hematoxylin & eosin (H&E) staining. The correlations among caspofungin, Pellino3 and necroptosis in I/R-treated brain or H/R-treated nerve cells were evaluated by biochemistry, molecular and gene overexpression assays. Results The I/R-treated brain showed the injuries (increase in neurological deficit score and infarct volume), downregulation of Pellino3, decreased ubiquitination of RIPK1 and up-regulation of necroptosis-associated proteins [RIPK1, RIPK3, mixed lineage kinase domain-like protein (MLKL), p-RIPK1, p-RIPK3 and p-MLKL]. Caspofungin treatment improved neurological function, reduced infarct volume, up-regulated Pellino3, increased RIPK1 ubiquitination and down-regulated levels of RIPK1, p-RIPK1, p-RIPK3 and p-MLKL. In PC12 cells, H/R treatment caused cellular injury (LDH release and necroptosis), downregulation of Pellino3, decreased ubiquitination of RIPK1 and up-regulation of necroptosis-associated proteins, these phenomena were reversed by overexpression of Pellino3. Conclusion Pellino3 has an important role in counteracting necroptosis via ubiquitination of RIPK1 and caspofungin can suppress the brain cell necroptosis in ischemic stroke via upregulation of Pellino3.

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Caspofungin suppresses zymosan-induced cytokine and chemokine release in THP-1 cells: possible involvement of the spleen tyrosine kinase pathway

Cited by 14 publications

References 44 publications

SYK Is Associated With Malignant Phenotype and Immune Checkpoints in Diffuse Glioma

SYK Is Associated With Malignant Phenotype and Immune Checkpoints in Diffuse Glioma

Visible-Light-Driven Photocatalytic Degradation of Tetracycline Using Heterostructured Cu₂O–TiO₂Nanotubes, Kinetics, and Toxicity Evaluation of Degraded Products on Cell Lines

Caspofungin suppresses brain cell necroptosis in the ischemic stroke rat via up-regulation of Pellino3

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Caspofungin suppresses zymosan-induced cytokine and chemokine release in THP-1 cells: possible involvement of the spleen tyrosine kinase pathway

Cited by 14 publications

References 44 publications

SYK Is Associated With Malignant Phenotype and Immune Checkpoints in Diffuse Glioma

SYK Is Associated With Malignant Phenotype and Immune Checkpoints in Diffuse Glioma

Visible-Light-Driven Photocatalytic Degradation of Tetracycline Using Heterostructured Cu2O–TiO2Nanotubes, Kinetics, and Toxicity Evaluation of Degraded Products on Cell Lines

Caspofungin suppresses brain cell necroptosis in the ischemic stroke rat via up-regulation of Pellino3

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Visible-Light-Driven Photocatalytic Degradation of Tetracycline Using Heterostructured Cu₂O–TiO₂Nanotubes, Kinetics, and Toxicity Evaluation of Degraded Products on Cell Lines