ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
IL-6 trans-signaling increases expression of airways disease genes in airway smooth muscle.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Neutrophil-mediated IL-6 receptor trans-signaling and the risk of chronic obstructive pulmonary disease and asthma.Human molecular genetics · 2017Pooled it
- The Dual Role of Interleukin-6 in the Pathophysiology of Skeletal Muscle: Mechanisms, Challenges, and Therapeutic Prospects.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Combining spatial and single-cell transcriptome data to analyze tertiary lymphoid structures in clear cell renal cell carcinoma reveals prognostic biomarkers.Journal of translational medicine · 2026Article
- Integrative Roles of Pro-Inflammatory Cytokines on Airway Smooth Muscle Structure and Function in Asthma.Immunological reviews · 2025Review
- A clinician's guide to effects of obesity on childhood asthma and into adulthood.Expert review of respiratory medicine · 2024Review
- Exploring redox imbalance and inflammation for asthma therapy.Molecular biology reports · 2023Review
- Levels of Soluble Interleukin 6 Receptor and Asp358Ala Are Associated With Cognitive Performance and Alzheimer Disease Biomarkers.Neurology(R) neuroimmunology & neuroinflammation · 2023Article
- Mechanistic Links Between Obesity and Airway Pathobiology Inform Therapies for Obesity-Related Asthma.Paediatric drugs · 2023Review
- Exploring the comorbidity mechanisms between asthma and idiopathic pulmonary fibrosis and the pharmacological mechanisms of Bu-Shen-Yi-Qi decoction therapy via network pharmacology.BMC complementary medicine and therapies · 2022Article
- Therapeutic Potential of Combining IL-6 and TNF Blockade in a Mouse Model of Allergic Asthma.International journal of molecular sciences · 2022Article
- Classical Signaling and Trans-Signaling Pathways Stimulated byInternational journal of molecular sciences · 2022Article
- TThe Journal of allergy and clinical immunology · 2022Article
- A genome-wide association study of quantitative computed tomographic emphysema in Korean populations.Scientific reports · 2021Article
- Nicotinic α7 acetylcholine receptor (α7nAChR) in human airway smooth muscle.Archives of biochemistry and biophysics · 2021Article
- Treatment options in type-2 low asthma.The European respiratory journal · 2021Review
- Therapeutic efficacy of IL-17A neutralization with corticosteroid treatment in a model of antigen-driven mixed-granulocytic asthma.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- TGF-β pathway activation by idiopathic pulmonary fibrosis (IPF) fibroblast derived soluble factors is mediated by IL-6 trans-signaling.Respiratory research · 2020Article
- Loki zupa alleviates inflammatory and fibrotic responses in cigarette smoke induced rat model of chronic obstructive pulmonary disease.Chinese medicine · 2020Article
- Thirty-eight-negative kinase 1 mediates trauma-induced intestinal injury and multi-organ failure.The Journal of clinical investigation · 2018Article
- Eosinophilic and Noneosinophilic Asthma.American journal of respiratory and critical care medicine · 2018Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Genetic data suggest that IL-6 trans-signaling may have a pathogenic role in the lung; however, the effects of IL-6 trans-signaling on lung effector cells have not been investigated. In this study, human airway smooth muscle (HASM) cells were treated with IL-6 (classical) or IL-6+sIL6R (trans-signaling) for 24 h and gene expression was measured by RNAseq. Intracellular signaling and transcription factor activation were assessed by Western blotting and luciferase assay, respectively. The functional effect of IL-6 trans-signaling was determined by proliferation assay. IL-6 trans-signaling had no effect on phosphoinositide-3 kinase and Erk MAP kinase pathways in HASM cells. Both classical and IL-6 trans-signaling in HASM involves activation of Stat3. However, the kinetics of Stat3 phosphorylation by IL-6 trans-signaling was different than classical IL-6 signaling. This was further reflected in the differential gene expression profile by IL-6 trans-signaling in HASM cells. Under IL-6 trans-signaling conditions 36 genes were upregulated, including PLA2G2A, IL13RA1, MUC1, and SOD2. Four genes, including CCL11, were downregulated at least twofold. The expression of 112 genes was divergent between IL-6 classical and trans-signaling, including the genes HILPDA, NNMT, DAB2, MUC1, WWC1, and VEGFA. Pathway analysis revealed that IL-6 trans-signaling induced expression of genes involved in regulation of airway remodeling, immune response, hypoxia, and glucose metabolism. Treatment of HASM cells with IL-6+sIL6R induced proliferation in a dose-dependent fashion, suggesting a role for IL-6 trans-signaling in asthma pathogenesis. These novel findings demonstrate differential effect of IL-6 trans-signaling on airway cells and identify IL-6 trans-signaling as a potential modifier of airway inflammation and remodeling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.