AI Article Synopsis
- Chronic inflammation is a significant factor in the development of cancer, with interleukin 33 (IL-33) being a key player in this process, though its environmental triggers remain unclear.
- A study reveals that the TLR3/4-TBK1-IRF3 signaling pathway links environmental stressors to the induction of IL-33 in skin and pancreatic inflammation.
- Pitavastatin, an FDA-approved drug, effectively reduces IL-33 levels and demonstrates the potential to prevent chronic pancreatitis and its associated cancer through inhibiting the TBK1 pathway, suggesting statins may be a promising approach to combat chronic inflammation-related cancers.
Article Abstract
Chronic inflammation is a major cause of cancer worldwide. Interleukin 33 (IL-33) is a critical initiator of cancer-prone chronic inflammation; however, its induction mechanism by environmental causes of chronic inflammation is unknown. Herein, we demonstrate that Toll-like receptor (TLR)3/4-TBK1-IRF3 pathway activation links environmental insults to IL-33 induction in the skin and pancreas inflammation. An FDA-approved drug library screen identifies pitavastatin to effectively suppress IL-33 expression by blocking TBK1 membrane recruitment/activation through the mevalonate pathway inhibition. Accordingly, pitavastatin prevents chronic pancreatitis and its cancer sequela in an IL-33-dependent manner. The IRF3-IL-33 axis is highly active in chronic pancreatitis and its associated pancreatic cancer in humans. Interestingly, pitavastatin use correlates with a significantly reduced risk of chronic pancreatitis and pancreatic cancer in patients. Our findings demonstrate that blocking the TBK1-IRF3-IL-33 signaling axis suppresses cancer-prone chronic inflammation. Statins present a safe and effective prophylactic strategy to prevent chronic inflammation and its cancer sequela.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11139893 | PMC |
| http://dx.doi.org/10.1038/s41467-024-48441-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Iron Regulatory Protein 2 (IRP2) Deficiency Is Protective Against Resistive Breathing-induced Pulmonary Inflammation.
Am J Respir Cell Mol Biol
January 2025
Lady Davis Institute for Medical Research, Montreal, Quebec, Canada;
Iron regulatory protein 2 (IRP2), a post-transcriptional regulator of cellular iron metabolism has been associated with susceptibility to chronic obstructive pulmonary disease (COPD). Resistive breathing (RB) is the hallmark of the pathophysiology of obstructive airway diseases, especially during exacerbations, where increased mechanical stress is imposed on the lung. We have previously shown that RB, through tracheal banding, mimicking severe airway obstruction, induces pulmonary inflammation and injury in previously healthy mice.
View Article and Find Full Text PDFPostoperative Adjuvant Dupilumab Improved Immediate Recovery in Patients With Advanced Type 2 Chronic Rhinosinusitis: An Exploratory Pilot Study.
Int Forum Allergy Rhinol
January 2025
Department of Otolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
NMR spectroscopy derived plasma biomarkers of inflammation in human populations: Influences of age, sex and adiposity.
PLoS One
January 2025
Australian National Phenome Center and Center for Computational and Systems Medicine, Health Futures Institute, Murdoch University, Perth, Western Australia, Australia.
Understanding the distribution and variation in inflammatory markers is crucial for advancing our knowledge of inflammatory processes and evaluating their clinical utility in diagnosing and monitoring acute and chronic disease. 1H NMR spectroscopy of blood plasma and serum was applied to measure a composite panel of inflammatory markers based on acute phase glycoprotein signals (GlycA and GlycB) and sub-regions of the lipoprotein derived Supramolecular Phospholipid Composite signals (SPC1, SPC2 and SPC3) to establish normal ranges in two healthy, predominantly white cohorts from Australia (n = 398) and Spain (n = 80; ages 20-70 years). GlycA, GlycB, SPC1 and SPC3 were not significantly impacted by age or sex, but SPC2 (an HDL-related biomarker) was significantly higher in women across all age ranges by an average of 33.
View Article and Find Full Text PDFObesity is a metabolic disease that is marked by excessive fat accumulation and is objectively defined as a body mass index (BMI) ≥30 kg/m2. Obesity is associated with several other comorbidities, including psoriasis, which is a chronic autoimmune skin disease. Adipocytes produce pro-inflammatory signaling molecules, namely adipokines and classic cytokines, that drive increased inflammation axnd may contribute to the pro-inflammatory pathways driving psoriasis disease pathogenesis.
View Article and Find Full Text PDFSpatial mapping of the HCC landscape identifies unique intratumoral perivascular-immune neighborhoods.
Hepatol Commun
November 2024
Human Immunology Laboratory, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.
Background: HCC develops in the context of chronic inflammation; however, the opposing roles the immune system plays in both the development and control of tumors are not fully understood. Mapping immune cell interactions across the distinct tissue regions could provide greater insight into the role individual immune populations have within tumors.
Methods: A 39-parameter imaging mass cytometry panel was optimized with markers targeting immune cells, stromal cells, endothelial cells, hepatocytes, and tumor cells.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!