ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Neutrophils activate alveolar macrophages by producing caspase-6-mediated cleavage of IL-1 receptor-associated kinase-M.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 36 citations in OpenAlex.
- The Intricate Role of Caspase-6 and Death Receptor-6 in Neurodegenerative Diseases.Cell biochemistry and biophysics · 2026Review
- Caspases and programmed cell death in sepsis: mechanisms, pathophysiology, and therapeutic targets.Frontiers in immunology · 2026Review
- Caspase 6 deficiency exacerbates inflammatory bowel disease via enterocyte necroptosis and bacterial translocation.Cell death discovery · 2025Article
- Regulation of inflammatory processes by caspases.Nature reviews. Molecular cell biology · 2025Review
- NUAK1 promotes metabolic dysfunction-associated steatohepatitis progression by activating Caspase 6-driven pyroptosis and inflammation.Hepatology communications · 2024Article
- Mutations in the Vicinity of the IRAK3 Guanylate Cyclase Center Impact Its Subcellular Localization and Ability to Modulate Inflammatory Signaling in Immortalized Cell Lines.International journal of molecular sciences · 2023Article
- Entamoeba histolytica exploits the autophagy pathway in macrophages to trigger inflammation in disease pathogenesis.Mucosal immunology · 2021Article
- Article
- Dietary phenotype and advanced glycation end-products predict WTC-obstructive airways disease: a longitudinal observational study.Respiratory research · 2021Observational
- Synergistic Effect of WTC-Particulate Matter and Lysophosphatidic Acid Exposure and the Role of RAGE: In-Vitro and Translational Assessment.International journal of environmental research and public health · 2020Article
- Newly Identified Function of Caspase-6 in ZBP1-mediated Innate Immune Responses, NLRP3 Inflammasome Activation, PANoptosis, and Host Defense.Journal of cellular immunology · 2020Article
- Constitutive ablation of caspase-6 reduces the inflammatory response and behavioural changes caused by peripheral pro-inflammatory stimuli.Cell death discovery · 2018Article
- Caspase-6 mediates resistance against Burkholderia pseudomallei infection and influences the expression of detrimental cytokines.PloS one · 2017Article
- Identification of Caspase-6 as a New Regulator of Alternatively Activated Macrophages.The Journal of biological chemistry · 2016Article
- Does Caspase-6 Have a Role in Perinatal Brain Injury?Developmental neuroscience · 2015Article
- The structure function of the death domain of human IRAK-M.Cell communication and signaling : CCS · 2014Article
- Extracellular caspase-6 drives murine inflammatory pain via microglial TNF-α secretion.The Journal of clinical investigation · 2014Article
- One airway: Biomarkers of protection from upper and lower airway injury after World Trade Center exposure.Respiratory medicine · 2014Article
- Lung cell-specific modulation of LPS-induced TLR4 receptor and adaptor localization.Communicative & integrative biology · 2014Review
- Maternal allergen exposure reprograms the developmental lung transcriptome in atopic and normoresponsive rat pups.American journal of physiology. Lung cellular and molecular physiology · 2012Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Alveolar macrophages (AMs) are exposed to respirable microbial particles. Similar to phagocytes in the gastrointestinal tract, AMs can suppress inflammation after exposure to nonpathogenic organisms. IL-1R-associated kinase-M (IRAK-M) is one inhibitor of innate immunity, normally suppressing pulmonary inflammation. During pneumonia, polymorphonuclear neutrophils (PMNs) are recruited by chemotactic factors released by AMs to produce an intense inflammation. We report that intact IRAK-M is strongly expressed in resting human AMs but is cleaved in patients with pneumonia via PMN-mediated induction of caspase-6 (CASP-6) activity. PMN contact is necessary and PMN membranes are sufficient for CASP-6 induction in macrophages. PMNs fail to induce TNF-α fully in macrophages expressing CASP-6 cleavage-resistant IRAK-M. Without CASP-6 expression, PMN stimulation fails to cleave IRAK-M, degrade IκBα, or induce TNF-α. CASP-6(-/-) mice subjected to cecal ligation and puncture have impaired TNF-α production in the lung and decreased mortality. LPS did not induce or require CASP-6 activity demonstrating that TLR2/4 signaling is independent from the CASP-6 regulated pathway. These data define a central role for CASP-6 in PMN-driven macrophage activation and identify IRAK-M as an important target for CASP-6. PMNs de-repress AMs via CASP-6-mediated IRAK-M cleavage. This regulatory system will blunt lung inflammation unless PMNs infiltrate the alveolar spaces.
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Registered trials
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.