Whole genome expression analysis in primary bronchial epithelial cells after exposure to sulphur mustard

Jowsey, Paul A.; Blain, Peter G.

doi:10.1016/j.toxlet.2014.08.001

Cited by 8 publications

(11 citation statements)

References 45 publications

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“…These include analyses of transcriptional responses of primary bronchial epithelial cells exposed to SM in vitro, lung tissue after intravenous administration of SM to rats, and lung tissue recovered from patients 25 years after exposure to SM. [24][25][26] While informative, these studies were limited as they were based on microarray analysis, which requires a priori selection of a predefined set of genes and offers reduced sensitivity and dynamic range when compared with RNA-seq. 27 In the present studies, we used RNA-seq to characterize the transcriptional response of lung macrophages to NM 1 and 28 days following exposure; our goal was to elucidate signaling pathways involved in regulating the acute and later resolution/profibrotic phases of the inflammatory response to lung injury.…”

Section: Discussionmentioning

confidence: 99%

“…Significant enrichment of these pathways in each study is likely driven by the prominent effect of mustards on DNA damage and p53-mediated responses. 24,25 The enrichment and predicted inhibition of apoptosis in lung macrophages after NM exposure may exacerbate injury and fibrosis, as it has been shown that increased resistance to apoptosis in both recruited and resident lung macrophages is involved in chronic inflammatory diseases and pulmonary fibrosis. 36,37 TNF was identified as the most significantly enriched upstream regulator 1 day post-NM exposure, and it exhibited the highest activation Z-score.…”

Section: Discussionmentioning

confidence: 99%

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Transcriptional profiling of lung macrophages during pulmonary injury induced by nitrogen mustard

Smith

Venosa

Gow

et al. 2020

Annals of the New York Academy of Sciences

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Nitrogen mustard (NM) and sulfur mustard are cytotoxic alkylating agents that cause severe and progressive damage to the respiratory tract. Evidence indicates that macrophages play a key role in the acute inflammatory phase and the later resolution/profibrotic phase of the pathogenic response. These diverse roles are mediated by inflammatory macrophages broadly classified as M1 proinflammatory and M2 anti-inflammatory that sequentially accumulate in the lung in response to injury. The goal of the present study was to identify signaling mechanisms contributing to macrophage activation in response to mustards. To accomplish this, we used RNA sequencing to analyze the gene expression profiles of lung macrophages isolated 1 and 28 days after intratracheal exposure of rats to NM (0.125 mg/kg) or phosphate-buffered saline control. We identified 641 and 792 differentially expressed genes 1 and 28 days post-NM exposure, respectively. These genes are primarily involved in processes related to cell movement and are regulated by cytokines, including tumor necrosis factor-α, interferon-γ, and interleukin-1β. Some of the most significantly enriched canonical pathways included STAT3 and NF-κB signaling. These cytokines and pathways may represent potential targets for therapeutic intervention to mitigate mustard-induced lung toxicity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Transcriptional profiling of lung macrophages during pulmonary injury induced by nitrogen mustard

Smith

Venosa

Gow

et al. 2020

Annals of the New York Academy of Sciences

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“…Pathway enrichment analysis indicated that these genes were mainly involved in a total of 36 pathways ( Figure 5 ). Many of these pathways were reported to be induced by SM in the previous studies, such as the MAPK signaling pathway [ 32 , 33 , 34 , 35 , 36 ], pathways in cancer [ 32 ], antigen processing and presentation [ 37 ], cell adhesion molecules (CAMs) [ 36 , 37 ], cell cycle [ 32 ], the p53 signaling pathway [ 32 , 36 ], vascular smooth muscle contraction [ 32 ], progesterone-mediated oocyte maturation [ 32 ], hematopoietic cell lineage [ 32 , 36 ], neuroactive ligand-receptor interaction [ 36 ], purine metabolism [ 32 , 36 ], chemokine signaling pathway [ 32 ], tight junction [ 32 ], bladder cancer [ 32 ] and amebiasis [ 32 ]. Oxidative stress and inflammation in vesicant-related injury were reported as major consequences of SM exposure [ 16 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

The Mixture of Salvianolic Acids from Salvia miltiorrhiza and Total Flavonoids from Anemarrhena asphodeloides Attenuate Sulfur Mustard-Induced Injury

Jianzhong

Chen

et al. 2015

IJMS

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Sulfur mustard (SM) is a vesicating chemical warfare agent used in numerous military conflicts and remains a potential chemical threat to the present day. Exposure to SM causes the depletion of cellular antioxidant thiols, mainly glutathione (GSH), which may lead to a series of SM-associated toxic responses. MSTF is the mixture of salvianolic acids (SA) of Salvia miltiorrhiza and total flavonoids (TFA) of Anemarrhena asphodeloides. SA is the main water-soluble phenolic compound in Salvia miltiorrhiza. TFA mainly includes mangiferin, isomangiferin and neomangiferin. SA and TFA possess diverse activities, including antioxidant and anti-inflammation activities. In this study, we mainly investigated the therapeutic effects of MSTF on SM toxicity in Sprague Dawley rats. Treatment with MSTF 1 h after subcutaneous injection with 3.5 mg/kg (equivalent to 0.7 LD50) SM significantly increased the survival levels of rats and attenuated the SM-induced morphological changes in the testis, small intestine and liver tissues. Treatment with MSTF at doses of 60 and 120 mg/kg caused a significant (p < 0.05) reversal in SM-induced GSH depletion. Gene expression profiles revealed that treatment with MSTF had a dramatic effect on gene expression changes caused by SM. Treatment with MSTF prevented SM-induced differential expression of 93.8% (973 genes) of 1037 genes. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 36 pathways, such as the MAPK signaling pathway, pathways in cancer, antigen processing and presentation. These data suggest that MSTF attenuates SM-induced injury by increasing GSH and targeting multiple pathways, including the MAPK signaling pathway, as well as antigen processing and presentation. These results suggest that MSTF has the potential to be used as a potential therapeutic agent against SM injuries.

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“…PubMed was searched for all messenger RNA (mRNA) microarray studies describing significantly upregulated gene expression in nonfetal lung cells or tissue in the setting of ALI, acute respiratory distress syndrome, pulmonary ischemia‐reperfusion, and/or primary pulmonary graft dysfunction. A total of 31 gene lists including 843 unique genes were identified from 23 articles . Based on the experimental models used in each study, these gene lists were subdivided into one of 3 “mechanical/noninfectious” categories (ischemia‐reperfusion, stretch, primary graft dysfunction) or one of 3 “toxic/infectious” categories (infection, sepsis, toxicity).…”

Section: Methodsmentioning

confidence: 99%

“…Genome‐wide microarray studies have previously demonstrated that ALI induces coordinated changes in the expression of hundreds of genes . We hypothesized that analyzing a representative subset of these previously described ALI‐related transcripts would allow for more precise, objective, and mechanistic evaluation of lung tissue injury and repair before, during, and after EVLP.…”

Section: Introductionmentioning

confidence: 99%

Ex vivo perfusion induces a time- and perfusate-dependent molecular repair response in explanted porcine lungs

Dromparis

Aboelnazar

Wagner

et al. 2019

American Journal of Transplantation

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Ex vivo lung perfusion (EVLP) shows promise in ameliorating pretransplant acute lung injury (ALI) and expanding the donor organ pool, but the mechanisms of ex vivo repair remain poorly understood. We aimed to assess the utility of gene expression for characterizing ALI during EVLP. One hundred sixty-nine porcine lung samples were collected in vivo (n = 25), after 0 (n = 11) and 12 (n = 11) hours of cold static preservation (CSP), and after 0 (n = 57), 6 (n = 8), and 12 (n = 57) hours of EVLP, utilizing various ventilation and perfusate strategies. The expression of 53 previously described ALI-related genes was measured and correlated with function and histology. Twenty-eight genes were significantly upregulated and 6 genes downregulated after 12 hours of EVLP. Aggregate gene sets demonstrated differential expression with EVLP (P < .001) but not CSP. Upregulated 28-gene set expression peaked after 6 hours of EVLP, whereas downregulated 6-gene set expression continued to decline after 12 hours. Cellular perfusates demonstrated a greater reduction in downregulated 6-gene set expression vs acellular perfusate (P < .038). Gene set expression correlated with relevant functional and histologic parameters, including P/F ratio (P < .001) and interstitial inflammation (P < .005). Further studies with posttransplant results are warranted to evaluate the clinical significance of this novel molecular approach for assessing organ quality during EVLP.

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Whole genome expression analysis in primary bronchial epithelial cells after exposure to sulphur mustard

Cited by 8 publications

References 45 publications

Transcriptional profiling of lung macrophages during pulmonary injury induced by nitrogen mustard

Transcriptional profiling of lung macrophages during pulmonary injury induced by nitrogen mustard

The Mixture of Salvianolic Acids from Salvia miltiorrhiza and Total Flavonoids from Anemarrhena asphodeloides Attenuate Sulfur Mustard-Induced Injury

Ex vivo perfusion induces a time- and perfusate-dependent molecular repair response in explanted porcine lungs

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