Evaluation of bronchoalveolar lavage fluid from ARDS patients with regard to apoptosis

Lee, Keu Sung; Choi, Young Hwa; Kim, Young Sun; Baik, Seung Hee; Oh, Yoon Sin; Sheen, Seung Soo; Park, Joo Hun; Hwang, Sung Chul; Park, Kwang Joo

doi:10.1016/j.rmed.2007.10.001

Cited by 45 publications

(44 citation statements)

References 38 publications

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“…Apoptosis of epithelial and endothelial cells has been observed in the lung of ARDS patients [40]. Apoptosis mediators are also increased in the BAL (bronchoalveolar lavage) fluid of ARDS patients [41]. A delayed apoptosis of intra-alveolar neutrophils with a concomitant increased apoptosis of alveolar epithelium increases the severity of lung injury [41].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA and mRNA expression profiling in rat acute respiratory distress syndrome

Huang

Xiao²,

Chintagari³

et al. 2014

BMC Med Genomics

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BackgroundAcute respiratory distress syndrome (ARDS) is characterized by pulmonary epithelial injury and extensive inflammation of the pulmonary parenchyma. Systematic analyses of microRNA (miRNA) and mRNA expression profiling in ARDS provide insights into understanding of molecular mechanisms of the pathogenesis of ARDS. The objective of this study was to identify miRNA and mRNA interactions in a rat model of ARDS by combining miRNA and mRNA microarray analyses.MethodsRat model of ARDS was induced by saline lavage and mechanical ventilation. The expression profiles of both mRNAs and miRNAs in rat ARDS model were performed by microarray analyses. Microarray data were further verified by quantitative RT-PCR. Functional annotation on dys-regulated mRNAs and miRNAs was carried out by bioinformatics analysis.ResultsThe expression of 27 miRNAs and 37 mRNAs were found to be significantly changed. The selected miRNAs and genes were further verified by quantitative real-time PCR. The down-regulated miRNAs included miR-24, miR-26a, miR-126, and Let-7a, b, c, f. The up-regulated miRNAs were composed of miR-344, miR-346, miR-99a, miR-127, miR-128b, miR-135b, and miR-30a/b. Gene ontology and functional annotation analyses indicated that up-regulated mRNAs, such as Apc, Timp1, and Sod2, were involved in the regulation of apoptosis. Bioinformatics analysis showed the inverse correlation of altered miRNAs with the expression of their predicted target mRNAs. While Sod2 was inversely correlated with Let-7a, b, c, f., Ebf1 and Apc were inversely correlated with miR-24 and miR-26a, respectively. miR-26a, miR-346, miR-135b, miR-30a/b, miR-344, and miR-18a targeted multiple altered mRNAs. Gabrb1, Sod2, Eif2ak1, Fbln5, and Tspan8 were targeted by multiple altered miRNAs.ConclusionThe expressions of miRNAs and mRNAs were altered in a rat model of ARDS. The identified miRNA-mRNA pairs may play critical roles in the pathogenesis of ARDS.

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Section: Discussionmentioning

confidence: 99%

MicroRNA and mRNA expression profiling in rat acute respiratory distress syndrome

Huang

Xiao²,

Chintagari³

et al. 2014

BMC Med Genomics

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“…Various stimuli may evoke complex “adaptive” responses to pathogens by neutrophils, by either decreasing (tolerance) or increasing (priming) activation [17,18]. Neutrophil function appears dysregulated in ARDS [19–26], and the potential exists that a beneficial adaptation to one microbe may place the host at a disadvantage against other infectious agents or inflammatory insults.…”

Section: Introductionmentioning

confidence: 99%

Extremes of Interferon-Stimulated Gene Expression Associate with Worse Outcomes in the Acute Respiratory Distress Syndrome

et al. 2016

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Acute Respiratory Distress Syndrome (ARDS) severity may be influenced by heterogeneity of neutrophil activation. Interferon-stimulated genes (ISG) are a broad gene family induced by Type I interferons, often as a response to viral infections, which evokes extensive immunomodulation. We tested the hypothesis that over- or under-expression of immunomodulatory ISG by neutrophils is associated with worse clinical outcomes in patients with ARDS. Genome-wide transcriptional profiles of circulating neutrophils isolated from patients with sepsis-induced ARDS (n = 31) and healthy controls (n = 19) were used to characterize ISG expression. Hierarchical clustering of expression identified 3 distinct subject groups with Low, Mid and High ISG expression. ISG accounting for the greatest variability in expression were identified (MX1, IFIT1, and ISG15) and used to analyze a prospective cohort at the Colorado ARDS Network site. One hundred twenty ARDS patients from four urban hospitals were enrolled within 72 hours of initiation of mechanical ventilation. Circulating neutrophils were isolated from patients and expression of ISG determined by PCR. Samples were stratified by standard deviation from the mean into High (n = 21), Mid, (n = 82) or Low (n = 17) ISG expression. Clinical outcomes were compared between patients with High or Low ISG expression to those with Mid-range expression. At enrollment, there were no differences in age, gender, co-existing medical conditions, or type of physiologic injury between cohorts. After adjusting for age, race, gender and BMI, patients with either High or Low ISG expression had significantly worse clinical outcomes than those in the Mid for number of 28-day ventilator- and ICU-free days (P = 0.0006 and 0.0004), as well as 90-day mortality and 90-day home with unassisted breathing (P = 0.02 and 0.004). These findings suggest extremes of ISG expression by circulating neutrophils from ARDS patients recovered early in the syndrome are associated with poorer clinical outcomes.

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“…(Beheshti et al, 2006;Emmler et al, 2007;Kuwano, 2008;Perl et al, 2008). In all of these cases, Fas and FasL are upregulated in the airway epithelial cells and are thought to contribute to cellular apoptosis (MatuteBello et al, 1999;Albertine et al, 2002;Hagimoto et al, 2002;Lee et al, 2008). The severity of the infection in septic ALI was highly correlated with the Fas-FasL system (Albertine et al, 2002); furthermore, acute respiratory distress syndrome nonsurvivors were shown to have markedly higher levels of FasL than survivors (Matute-Bello et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Postexposure Application of Fas Receptor Small-Interfering RNA to Suppress Sulfur Mustard–Induced Apoptosis in Human Airway Epithelial Cells: Implication for a Therapeutic Approach

Keyser

Andres

Nealley

et al. 2012

J Pharmacol Exp Ther

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Sulfur mustard (SM) is a vesicant chemical warfare and terrorism agent. Besides skin and eye injury, respiratory damage has been mainly responsible for morbidity and mortality after SM exposure. Previously, it was shown that suppressing the death receptor (DR) response by the dominant-negative Fas-associated death domain protein prior to SM exposure blocked apoptosis and microvesication in skin. Here, we studied whether antagonizing the Fas receptor (FasR) pathway by small-interfering RNA (siRNA) applied after SM exposure would prevent apoptosis and, thus, airway injury. Normal human bronchial/tracheal epithelial (NHBE) cells were used as an in vitro model with FasR siRNA, FasR agonistic antibody CH11, and FasR antagonistic antibody ZB4 as investigative tools. In NHBE cells, both SM (300 mM) and CH11 (100 ng/ml) induced caspase-3 activation, which was inhibited by FasR siRNA and ZB4, indicating that SM-induced apoptosis was via the Fas response. FasR siRNA inhibited SMinduced caspase-3 activation when added to NHBE cultures up to 8 hours after SM. Results using annexin V/propidium iodidestained cells showed that both apoptosis and necrosis were involved in cell death due to SM; FasR siRNA decreased both apoptotic and necrotic cell populations. Bronchoalveolar lavage fluid (BALF) of rats exposed to SM (1 mg/kg, 50 minutes) revealed a significant (P , 0.05) increase in soluble Fas ligand and active caspase-3 in BALF cells. These findings suggest an intervention of Fas-mediated apoptosis as a postexposure therapeutic strategy with a therapeutic window for SM inhalation injury and possibly other respiratory diseases involving the Fas response.

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Evaluation of bronchoalveolar lavage fluid from ARDS patients with regard to apoptosis

Abstract: Among the mediators in BAL fluid from ARDS patients, G-CSF had the most significant prognostic implications, and the sFas and TRAIL levels were correlated with clinical severity.

Cited by 45 publications

References 38 publications

MicroRNA and mRNA expression profiling in rat acute respiratory distress syndrome

MicroRNA and mRNA expression profiling in rat acute respiratory distress syndrome

Extremes of Interferon-Stimulated Gene Expression Associate with Worse Outcomes in the Acute Respiratory Distress Syndrome

Postexposure Application of Fas Receptor Small-Interfering RNA to Suppress Sulfur Mustard–Induced Apoptosis in Human Airway Epithelial Cells: Implication for a Therapeutic Approach

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