Oncostatin M expression induced by bacterial triggers drives airway inflammatory and mucus secretion in severe asthma

Headland, Sarah E.; Dengler, Hart S.; Xu, Daqi; Teng, Grace; Everett, Christine; Ratsimandresy, Rojo A.; Yan, Donghong; Kang, Jing; Ganeshan, Kirthana; Nazarova, Evgeniya V.; Gierke, Sarah; Wedeles, Christopher J.; Guidi, Riccardo; DePianto, Daryle J.; Morshead, Katrina B.; Huynh, Alison; Mills, Jessica; Flanagan, Sean; Hambro, Shannon; Núñez, Víctor; Klementowicz, Joanna E.; Shi, Yongchang; Wang, Jianyong; Bevers, Jack; Ramirez-Carrozzi, Vladimir; Pappu, Rajita; Abbas, Alexander R.; Heiden, Jason A. Vander; Choy, David F.; Yadav, Rajbharan; Modrušan, Zora; Panettieri, Reynold A.; Koziol‐White, Cynthia; Jester, William F.; Jenkins, Brendan J.; Cao, Yi; Clarke, Christine L.; Austin, Cary D.; Lafkas, Daniel; Xu, Min; Wolters, Paul J.; Arron, Joseph R.; West, N.; Wilson, Mark S.

doi:10.1126/scitranslmed.abf8188

Cited by 25 publications

(9 citation statements)

References 82 publications

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“…This notion could be inferred from a prior report describing higher levels of OSM in patients with combined COVID‐19 and bacterial infections from those with COVID‐19 alone 21 . Similar observations were also reported in patients with severe asthma, as their OSM levels elevated when they attracted bacterial infections 22 …”

Section: Discussionsupporting

confidence: 78%

“…21 Similar observations were also reported in patients with severe asthma, as their OSM levels elevated when they attracted bacterial infections. 22 Collectively, the information generated in this study might assist the process of patient selection prior to the initiation of ECMO support. Furthermore, the trajectory of pOSM levels after initiating ECMO could help guide end-of-life decisions and address the chances of survival with patients and their families.…”

Section: Discussionmentioning

confidence: 95%

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Oncostatin M for characterizing the inflammatory burden and outcome of V‐V ECMO in ARDS patients

et al. 2023

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BackgroundAssessing the outcome of Veno‐Venous Extracorporeal Membrane Oxygenation (V‐V ECMO) support remains challenging as plasma lactate (pLA), the widely used tool for this purpose, has been shown unreliable. We hypothesized that plasma oncostatin M (pOSM), a sensitive marker of leukocyte activation in infection and inflammation, could address this deficiency.MethodsPlasma OSM levels were measured by ELISA in 30 Acute Respiratory Distress Syndrome (ARDS) patients, prior to cannulation (baseline) and decannulation.ResultsBased on the absolute pOSM levels at presentation, patients were separated into two groups, A and B. Patients in group A had low pOSM levels (Mean ± SD; Median, 1.1 ± 3.8; 0 pg/mL), whereas group B had high pOSM levels (1548 ± 1999; 767 pg/mL) [t‐test: p < 0.01]. The percentage of pOSM levels at decannulation relative to baseline OSM levels was significantly higher in those who died (116.8 ± 68.0; 85.3%) than those who survived (47.6 ± 25.5; 48.9%) [t‐test: p = 0.02; Mann–Whitney U Test: p = 0.01]. Conversely, no significant difference was observed in the percentage of pLA levels between those who died (142.9 ± 179.9; 89.8%) and those who survived (79.3 ± 34.3; 81.8%) [t‐test: p = 0.31; Mann–Whitney U Test: p = 0.63].ConclusionThese early findings suggested critical value of absolute and relative pOSM to characterize the inflammatory burden of ARDS patients and the outcome of their V‐V ECMO support.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 95%

Oncostatin M for characterizing the inflammatory burden and outcome of V‐V ECMO in ARDS patients

et al. 2023

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“…Several of these proteins were strongly associated with asthma progression and were reported to be significantly altered in serum. , Among them, IL-6, a biomarker of systemic inflammation, was proved to be elevated in the serum and airways of asthmatic patients. , The IL-6 family cytokines has recently been found to be increased in the plasma of patients with severe asthma associated with obesity and blood neutrophilia, possibly originated from increased production by inflammatory macrophages in the adipose tissue of obese patients. , OSM induced by bacterial dysregulation triggers asthma-related symptoms, including airway inflammation and mucus secretion. Blocking OSM with antibodies reduces the symptoms associated with severe asthma in mice after exposure to bacterial stimuli . OSM enhanced MC growth through fibroblast-dependent pathway in mice .…”

Section: Discussionmentioning

confidence: 99%

IL18R1-Related Molecules as Biomarkers for Asthma Severity and Prognostic Markers for Idiopathic Pulmonary Fibrosis

Lin,

Wang,

Tang

et al. 2023

J. Proteome Res.

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To determine the role of inflammation-related proteins in predicting asthma severity and outcome, 92 inflammation-related proteins were measured in the asthmatic serum using Olink analysis. Different bioinformatics algorithms were developed to cross analyze with the single-cell or transcriptome data sets from the Gene Expression Omnibus database to explore the role of IL18R1 and related genes in asthma and idiopathic pulmonary fibrosis (IPF). Olink identified 52 differentially expressed proteins in asthma. They were strongly linked to the cytokine–cytokine receptor interaction, TNF, and NF-κB signaling pathway. Seven proteins were found in both single-cell RNA and Olink analyses. Among them, IL18R1 was predominantly expressed in mast cells, and the results suggested enhanced communication between mast cells and CD 8+ T cells. IL18R1 was upregulated in serum and induced sputum and bronchoalveolar lavage fluid of patients with uncontrolled or severe asthma. IL18R1 was positively correlated with TNFSF1 and OSM and S100A12. The diagnostic efficacy of these serum IL18R1-related molecules for asthma ranged from 0.839 to 0.921. Moreover, high levels of IL18R1, TNFSF1, OSM, and S100A12 were significantly associated with shorter survival times and worse lung function. IL18R1-related molecules may serve as biomarkers for monitoring uncontrolled or severe asthma and as prognostic markers for IPF.

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“…Previous studies have described both pro- and anti-inflammatory roles for OSM ( 35 – 37 ). As Osm is induced in response to a variety of cues, it is possible that the tissue context of induction may shape the role of OSM.…”

Section: Discussionmentioning

confidence: 99%

Macrophages control pathological interferon responses during viral respiratory infection

Hoagland,

Rodríguez-Morales,

Mann

et al. 2023

Preprint

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Antiviral immune mediators, including interferons and their downstream effectors, are critical for host defense yet can become detrimental when uncontrolled. Here, we identify a macrophage-mediated anti-inflammatory mechanism that limits type I interferon (IFN-I) responses. Specifically, we found that cellular stress and pathogen recognition induce Oncostatin M (OSM) production by macrophages. OSM-deficient mice succumbed to challenge with influenza or a viral mimic due to heightened IFN-I activation. Macrophage-derived OSM restricted excessive IFN-I production by lung epithelial cells following viral stimulation. Furthermore, reconstitution of OSM in the respiratory tract was sufficient to protect mice lacking macrophage-derived OSM against morbidity, indicating the importance of local OSM production. This work reveals a host strategy to dampen inflammation in the lung through the negative regulation of IFN-I by macrophages.One-Sentence SummaryType I interferons induced by viral stimuli are negatively regulated by macrophage-derived Oncostatin M.

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Oncostatin M expression induced by bacterial triggers drives airway inflammatory and mucus secretion in severe asthma

Abstract: Bacterial-associated LPS drives oncostatin M–dependent airway inflammation and mucus hypersecretion in severe asthma.

Cited by 25 publications

References 82 publications

Oncostatin M for characterizing the inflammatory burden and outcome of V‐V ECMO in ARDS patients

Oncostatin M for characterizing the inflammatory burden and outcome of V‐V ECMO in ARDS patients

IL18R1-Related Molecules as Biomarkers for Asthma Severity and Prognostic Markers for Idiopathic Pulmonary Fibrosis

Macrophages control pathological interferon responses during viral respiratory infection

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