Expression Levels of Eosinophil Granule Protein mRNAs in Induced Sputum Reflect Airway Hyperresponsiveness and Airflow Limitation

Jung, Jae-Woo; Kang, Hye-Ryun; Lee, Hyunseung; Park, Heung-Woo; Cho, Sang Heon; Min, Kyung-Up; Sohn, Seong-Wook

doi:10.1620/tjem.233.49

Cited by 12 publications

(7 citation statements)

References 26 publications

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“…Other factors, including lysis time and temperature, affect the concentrations of the in ammatory biomarker in the induced sputum supernatant. Studies have shown that the measurement of mRNA expression may be a more sensitive method of evaluating in ammatory mediators in induced sputum [7,39,40]. In accordance with this, our analysis also showed that sputum cell CC16 mRNA but not protein expression in the sputum supernatant was closely and independently correlated with lung function decline (FEV1%pred and FEV1%FVC) in patients with COPD.…”

Section: Discussionsupporting

confidence: 87%

Inflammatory Biomarkers in induced Sputum Predict Chronic Obstructive Pulmonary Disease (COPD) Severity

He¹,

Deng²,

Jia³

et al. 2020

Preprint

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Background: The progression of an abnormal inflammatory response plays a crucial role in the functional decline that occurs in COPD patients[1].Compared to serum biomarkers, inflammatory biomarkers in induced sputum would be a more reliable reflection of the inflammatory processes in the airways. Based on this, we explored the association of inflammatory biomarkers in induced sputum with lung function in COPD patients.Methods: 102 patients with COPD were recruited and underwent spirometry. According to the percentage of the predicted forced expiratory volume in 1 second value (FEV1%pred), participants with COPD were divided into a mild and moderate group (FEV1%pred≥ 50%, n=57) and a severe and extremely severe group (FEV1%pred<50%, n=45). Then we analyzed a series of inflammatory biomarkers in induced sputum and determined their association with lung function in COPD patients.Results: We found an increased levels of eosinophils percentage, MMP9 mRNA, LTB4R mRNA, and decreased levels of CC16 mRNA and miR-155 in the induced sputum of patients with severe and extremely severe COPD. In our analysis, sputum cell CC16 mRNA expression, but not CC16 secretion in the supernatant of the sputum, was closely and independently correlated with lung function decline in patients with COPD. Conclusion: The levels of numerous inflammatory biomarkers in induced sputum were associated with lung function decline in COPD，and the relative CC16 mRNA expression level with a cutoff of 1.09 could be a predictive biomarker of the severity of COPD.

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Section: Discussionsupporting

confidence: 87%

Inflammatory Biomarkers in induced Sputum Predict Chronic Obstructive Pulmonary Disease (COPD) Severity

He¹,

Deng²,

Jia³

et al. 2020

Preprint

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“…Induced sputum was processed as previously described 19 . The cell pellet was mixed with TRIzol (Gibco) to extract the RNA before RT‐PCR was performed using a RT‐PCR kit (Promega).…”

Section: Methodsmentioning

confidence: 99%

“…Induced sputum was processed as previously described. 19 The cell pellet was mixed with TRIzol (Gibco) to extract the RNA before RT‐PCR was performed using a RT‐PCR kit (Promega). The mRNA of TG2, CD206, macrophage galactose‐type C‐type lectin 1 (MGL), and Arg1 was amplified on an ABI 7500 real‐time PCR system, using SYBR Green master mix (Applied Biosystems).…”

Section: Methodsmentioning

confidence: 99%

Tranglutaminase 2 contributes to the asthmatic inflammation by modulating activation of alveolar macrophages

Lee

Park

Bae

et al. 2021

Immunity Inflam & Disease

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Background Transglutaminase 2 (TG2), a multifunctional calcium‐dependent acyltransferase, is upregulated in asthmatic airways and reported to play a role in the pathogenesis of allergic asthma. However, the underlying mechanism is not fully understood. Objective To investigate the role of TG2 in alternative activation of alveolar macrophages by using murine asthma model. Methods TG2 expression was assessed in induced sputum of 21 asthma patients and 19 healthy controls, and lung tissue of ovalbumin (OVA)‐induced murine asthma model. To evaluate the role of TG2 in asthma, we developed an OVA asthma model in both TG2 null and wild‐type mice. The expression of M2 macrophage markers was measured by fluorescence‐activated cell sorting (FACS) after OVA sensitization and challenge. To evaluate the effect of TG2 inhibition in vitro, interleukin 4 (IL‐4) or IL‐13‐stimulated expression of M2 macrophage markers was measured in CRL‐2456 cells in the presence and absence of a TG2 inhibitor. Results The expression of both TG2 and M2 markers was increased in the sputum of asthmatics compared with that of healthy controls. The expression of TG2 was increased in macrophages of OVA mice. Airway hyperresponsiveness, and the number of inflammatory cells, including eosinophils, was significantly reduced in TG2 null mice compared with wild‐type mice. Enhanced expression of M2 markers in OVA mice was normalized by TG2 knockout. IL‐4 or IL‐13‐stimulated expression of M2 markers in alveolar macrophages was also attenuated by TG2 inhibitor treatment in vitro. Conclusion Our results suggest that TG2‐mediated modulation of alveolar macrophage polarization plays important roles in the pathogenesis of asthma.

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“…We followed a standardized method to obtain induced sputum samples [14]. Sputum samples that contained squamous epithelial cells less than 20% of the total cell count were considered appropriate [15]. We collected at least 0.2 g of stool samples in a stool container (SPL Life Sciences, Pocheon-si, Korea).…”

Section: Samples and Clinical Parametersmentioning

confidence: 99%

Peripheral blood transcriptomic clusters uncovered immune phenotypes of asthma

et al. 2022

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Background Transcriptomic analysis has been used to elucidate the complex pathogenesis of heterogeneous disease and may also contribute to identify potential therapeutic targets by delineating the hub genes. This study aimed to investigate whether blood transcriptomic clustering can distinguish clinical and immune phenotypes of asthmatics, and microbiome in asthmatics. Methods Transcriptomic expression of peripheral blood mononuclear cells (PBMCs) from 47 asthmatics and 21 non-asthmatics was measured using RNA sequencing. A hierarchical clustering algorithm was used to classify asthmatics. Differentially expressed genes, clinical phenotypes, immune phenotypes, and microbiome of each transcriptomic cluster were assessed. Results In asthmatics, three distinct transcriptomic clusters with numerously different transcriptomic expressions were identified. The proportion of severe asthmatics was highest in cluster 3 as 73.3%, followed by cluster 2 (45.5%) and cluster 1 (28.6%). While cluster 1 represented clinically non-severe T2 asthma, cluster 3 tended to include severe non-T2 asthma. Cluster 2 had features of both T2 and non-T2 asthmatics characterized by the highest serum IgE level and neutrophil-dominant sputum cell population. Compared to non-asthmatics, cluster 1 showed higher CCL23 and IL1RL1 expression while the expression of TREML4 was suppressed in cluster 3. CTSD and ALDH2 showed a significant positive linear relationship across three clusters in the order of cluster 1 to 3. No significant differences in the diversities of lung and gut microbiomes were observed among transcriptomic clusters of asthmatics and non-asthmatics. However, our study has limitations in that small sample size data were analyzed with unmeasured confounding factors and causal relationships or function pathways were not verified. Conclusions Genetic clustering based on the blood transcriptome may provide novel immunological insight, which can be biomarkers of asthma immune phenotypes. Trial registration Retrospectively registered

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Expression Levels of Eosinophil Granule Protein mRNAs in Induced Sputum Reflect Airway Hyperresponsiveness and Airflow Limitation

Cited by 12 publications

References 26 publications

Inflammatory Biomarkers in induced Sputum Predict Chronic Obstructive Pulmonary Disease (COPD) Severity

Inflammatory Biomarkers in induced Sputum Predict Chronic Obstructive Pulmonary Disease (COPD) Severity

Tranglutaminase 2 contributes to the asthmatic inflammation by modulating activation of alveolar macrophages

Peripheral blood transcriptomic clusters uncovered immune phenotypes of asthma

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