ArticlePloS one2016
Full Spectrum of LPS Activation in Alveolar Macrophages of Healthy Volunteers by Whole Transcriptomic Profiling.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Hesperetin alleviates sepsis-associated acute respiratory distress syndrome via the PI3K/Akt/PTEN axis.Scientific reports · 2026Article
- DIG-DUBs: mechanisms and functions of ISG15 deconjugation by human and viral cross-reactive ubiquitin proteases.Biochemical Society transactions · 2025Article
- Absence of c-Maf and IL-10 enables type I IFN enhancement of innate responses to LPS in alveolar macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Targeting of TAMs: can we be more clever than cancer cells?Cellular & molecular immunology · 2024Review
- Human Alveolar and Monocyte-Derived Human Macrophage Responses to Mycobacterium tuberculosis.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Mechanisms of USP18 deISGylation revealed by comparative analysis with its human paralog USP41.bioRxiv : the preprint server for biology · 2024Article
- Absence of c-Maf and IL-10 enables Type I IFN enhancement of innate responses to low-dose LPS in alveolar macrophages.bioRxiv : the preprint server for biology · 2024Article
- BATF2 enhances proinflammatory cytokine responses in macrophages and improves early host defense against pulmonaryAmerican journal of physiology. Lung cellular and molecular physiology · 2023Article
- Dexamethasone impairs the expression of antimicrobial mediators in lipopolysaccharide-activated primary macrophages by inhibiting both expression and function of interferon β.Frontiers in immunology · 2023Article
- Transcriptomic signatures reveal a shift towards an anti-inflammatory gene expression profile but also the induction of type I and type II interferon signaling networks through aryl hydrocarbon receptor activation in murine macrophages.Frontiers in immunology · 2023Article
- Article
- Mechanoimmunology: Are inflammatory epigenetic states of macrophages tuned by biophysical factors?APL bioengineering · 2022Review
- Liver macrophages and inflammation in physiology and physiopathology of non-alcoholic fatty liver disease.The FEBS journal · 2022Review
- Effects of equine SALSA on neutrophil phagocytosis and macrophage cytokine production.PloS one · 2022Article
- How Macrophages Become Transcriptionally Dysregulated: A Hidden Impact of Antitumor Therapy.International journal of molecular sciences · 2021Review
- Stressed erythrophagocytosis induces immunosuppression during sepsis through heme-mediated STAT1 dysregulation.The Journal of clinical investigation · 2021Article
- Single cell RNA sequencing identifies an early monocyte gene signature in acute respiratory distress syndrome.JCI insight · 2020Article
- Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages.Cancers · 2020Review
- FOXO3a is stabilized by USP18-mediated de-ISGylation and inhibits TGF-β1-induced fibronectin expression.Journal of investigative medicine : the official publication of the American Federation for Clinical Research · 2020Article
- The role of deubiquitinating enzymes in gastric cancer.Oncology letters · 2020Review
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Authors and funding
17 authors.
Funding
Abstract
Despite recent advances in understanding macrophage activation, little is known regarding how human alveolar macrophages in health calibrate its transcriptional response to canonical TLR4 activation. In this study, we examined the full spectrum of LPS activation and determined whether the transcriptomic profile of human alveolar macrophages is distinguished by a TIR-domain-containing adapter-inducing interferon-β (TRIF)-dominant type I interferon signature. Bronchoalveolar lavage macrophages were obtained from healthy volunteers, stimulated in the presence or absence of ultrapure LPS in vitro, and whole transcriptomic profiling was performed by RNA sequencing (RNA-Seq). LPS induced a robust type I interferon transcriptional response and Ingenuity Pathway Analysis predicted interferon regulatory factor (IRF)7 as the top upstream regulator of 89 known gene targets. Ubiquitin-specific peptidase (USP)-18, a negative regulator of interferon α/β responses, was among the top up-regulated genes in addition to IL10 and USP41, a novel gene with no known biological function but with high sequence homology to USP18. We determined whether IRF-7 and USP-18 can influence downstream macrophage effector cytokine production such as IL-10. We show that IRF-7 siRNA knockdown enhanced LPS-induced IL-10 production in human monocyte-derived macrophages, and USP-18 overexpression attenuated LPS-induced production of IL-10 in RAW264.7 cells. Quantitative PCR confirmed upregulation of USP18, USP41, IL10, and IRF7. An independent cohort confirmed LPS induction of USP41 and IL10 genes. These results suggest that IRF-7 and predicted downstream target USP18, both elements of a type I interferon gene signature identified by RNA-Seq, may serve to fine-tune early cytokine response by calibrating IL-10 production in human alveolar macrophages.
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