Sodium azide suppresses LPS-induced expression MCP-1 through regulating IκBζ and STAT1 activities in macrophages

Park, Cho-Yi; Heo, Jae-Nyoung; Suk, Kyoungho; Lee, Won‐Ha

doi:10.1016/j.cellimm.2017.02.007

Cited by 11 publications

(5 citation statements)

References 63 publications

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“…Several of the observed links showed strong literature precedence. For example, the gene lactotransferrin was linked to Aeromonas [31], Burkholderia was linked to gene MUC6 [32], Haemophilus was linked to NFKB Inhibitor Zeta [33], and Pasteurella was linked to IL1B [34]. To the best of our knowledge, several novel links were also found, such as between Haemophilus and IL1B and between Candida and GCSAML.…”

Section: Cross-talk Between Genes and Microbes Defined By Lda-linkmentioning

confidence: 85%

“…Burkholderia, a gram-negative bacterial genus, is recognized as an important pathogen in the mucus-filled lungs of patients with cystic fibrosis; it was linked to gene MUC6, which encodes a secreted protein responsible for the production of mucin [32]. Classical pathogenic-type interactions included Haemophilus linked to NFKB inhibitor zeta, which is induced by the bacterial cell wall component lipopolysaccharide [33]. In addition, Haemophilus was linked to the cytokine interleukin 1 beta (IL1B), an important mediator of the inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

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Faculty Opinions recommendation of Approaches for integrating heterogeneous RNA-seq data reveal cross-talk between microbes and genes in asthmatic patients.

Schäffer

2020

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature

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Sputum induction is a non-invasive method to evaluate the airway environment, particularly for asthma. RNA sequencing (RNA-seq) of sputum samples can be challenging to interpret due to the complex and heterogeneous mixtures of human cells and exogenous (microbial) material. In this study, we develop a pipeline that integrates dimensionality reduction and statistical modeling to grapple with the heterogeneity. LDA(Latent Dirichlet allocation)-link connects microbes to genes using reduced-dimensionality LDA topics. We validate our method with single-cell RNA-seq and microscopy and then apply it to the sputum of asthmatic patients to find known and novel relationships between microbes and genes.

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Section: Cross-talk Between Genes and Microbes Defined By Lda-linkmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Faculty Opinions recommendation of Approaches for integrating heterogeneous RNA-seq data reveal cross-talk between microbes and genes in asthmatic patients.

Schäffer

2020

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature

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“…Macrophages were activated by lipopolysaccharide (LPS) (#L2880, Sigma-aldrich, Germany) to establish an in vitro sepsis model as previously described. 21 RAW 264.7 cells were cultured in serum-free Opti-MEM (Gibco, Brooklyn, NY, USA) 1 h before transfection with ADAR1-overexpressing adenovirus (GenePharma), ADRA1-small interfering RNA (siRNA) (RiboBio, Guangzhou, China), an miR-122 mimic, an miR-122 inhibitor (RiboBio), or a negative control using Lipofectamine 3000 transfection reagent (Invitrogen, Waltham, MA, USA) according to the manufacturer’s instructions. The cells were treated with LPS for another 24 h after transfection and collected for subsequent experiments 12 h after the LPS treatment ended.…”

Section: Methodsmentioning

confidence: 99%

ADAR1 Inhibits Macrophage Apoptosis and Alleviates Sepsis-induced Liver Injury Through miR-122/BCL2A1 Signaling

Liu,

Xie,

Duan

et al. 2023

J Clin Transl Hepatol

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Background and Aims As sepsis progresses, immune cell apoptosis plays regulatory roles in the pathogenesis of immunosuppression and organ failure. We previously reported that adenosine deaminases acting on RNA-1 (ADAR1) reduced intestinal and splenic inflammatory damage during sepsis. However, the roles and mechanism of ADAR1 in sepsis-induced liver injury remain unclear. Methods We performed transcriptome and single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from patients with sepsis to investigate the effects of ADAR1 on immune cell activities. We also employed a cecal ligation and puncture (CLP) sepsis mouse model to evaluate the roles of ADAR1 in sepsis-induced liver injury. Finally, we treated murine RAW 264.7 macrophages with lipopolysaccharide to explore the underlying ADAR1-mediated mechanisms in sepsis. Results PBMCs from patients with sepsis had obvious apoptotic morphological features. Single-cell RNA sequencing indicated that apoptosis-related pathways were enriched in monocytes, with significantly elevated ADAR1 and BCL2A1 expression in severe sepsis. CLP-induced septic mice had aggravated liver injury and Kupffer cell apoptosis that were largely alleviated by ADAR1 overexpression. ADAR1 directly bound to pre-miR-122 to modulate miR-122 biosynthesis. miR-122 was an upstream regulator of BCL2A1. Furthermore, ADAR1 also reduced macrophage apoptosis in mice with CLP-induced sepsis through the miR-122/BCL2A1 signaling pathway and protected against sepsis-induced liver injury. Conclusions The findings show that ADAR1 alleviates macrophage apoptosis and sepsis-induced liver damage through the miR-122/BCL2A1 signaling pathway. The study provides novel insights into the development of therapeutic interventions in sepsis.

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“…MCP-1 is a vital inflammatory mediator in LPS-treated cells. [22,23] MCP-1 (Figure 5A) was markedly upregulated in T24 cells by LPS treatment but was signally downregulated by 10 and 20 μM Oxybutynin. Moreover, the MCP-1 protein level (Figure 5B) was elevated from 38.7 to 81.2 pg/mL by LPS treatment, then repressed to 63.2 and 49.2 pg/mL by 10 and 20 μM Oxybutynin, respectively.…”

Section: Oxybutynin Suppressed the Expression Of Mcp-1 In Human Bladd...mentioning

confidence: 99%

Oxybutynin ameliorates LPS‐induced inflammatory response in human bladder epithelial cells

Chen,

Li,

Wang

et al. 2023

J Biochem & Molecular Tox

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Urinary tract infection (UTI) mainly results from bacterial infections in the urinary tract and markedly impacts the normal lives of millions of patients worldwide. The infection and damage to urethral epithelial cells is the first and key step of UTI development and is a critical target for treating clinical UTI. Oxybutynin, an agent for treating urinary incontinence, is recently claimed with protective effects on bladder ultrastructure. Our study will assess the impact of Oxybutynin on inflammation in lipopolysaccharide (LPS)‐stimulated bladder epithelial cells. Bladder epithelial T24 cells were treated with 1 μg/mL LPS with or without 10 and 20 μM Oxybutynin for 24 h. Increased levels of oxidative stress (OS) biomarkers, such as reactive oxygen species, 8‐hydroxy‐2'‐deoxyguanosine, malondialdehyde, as well as upregulated inducible nitric oxide synthase and promoted release of nitric oxide, were observed in LPS‐managed T24 cells, all of which were signally suppressed by Oxybutynin. Furthermore, severe inflammatory responses, including enhanced release of cytokines, upregulated matrix metallopeptidase‐2 (MMP‐2) and MMP‐9, and raised monocyte chemoattractant protein‐1 level, were found in LPS‐challenged T24 cells, which were markedly reversed by Oxybutynin. Moreover, the activated toll‐1ike receptor 4/nuclear factor‐κB pathway observed in LPS‐managed T24 cells was repressed by Oxybutynin. Collectively, Oxybutynin mitigated LPS‐induced inflammatory response in human bladder epithelial cells.

show abstract

Sodium azide suppresses LPS-induced expression MCP-1 through regulating IκBζ and STAT1 activities in macrophages

Cited by 11 publications

References 63 publications

Faculty Opinions recommendation of Approaches for integrating heterogeneous RNA-seq data reveal cross-talk between microbes and genes in asthmatic patients.

Faculty Opinions recommendation of Approaches for integrating heterogeneous RNA-seq data reveal cross-talk between microbes and genes in asthmatic patients.

ADAR1 Inhibits Macrophage Apoptosis and Alleviates Sepsis-induced Liver Injury Through miR-122/BCL2A1 Signaling

Oxybutynin ameliorates LPS‐induced inflammatory response in human bladder epithelial cells

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