AI Article Synopsis
Article Abstract
Tumor promoters such as the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) are proinflammatory agents, and their mechanism of action in epithelial carcinogenesis has been linked to the release of IL-1 alpha and the induction of chronic inflammation in skin. To test the role of IL-1 alpha and inflammation in models of cutaneous carcinogenesis, we used our previously described FVB/N transgenic mice overexpressing 17-kDa IL-1 alpha in the epidermis under the keratin 14 (K14) promoter. Strikingly, the K14/IL-1 alpha mice were completely resistant to papilloma and carcinoma formation induced by a two-stage DMBA/TPA protocol, while littermate controls developed both tumor types. K14/IL-1 alpha mice crossed with the highly sensitive TG.AC mice, constitutively expressing mutant Ha-Ras, also failed to develop papillomas or carcinomas. When the K14/IL-1 alpha transgene was bred onto a recombinase-activating gene-2-deficient background, the resistance persisted, indicating that innate, but not acquired, mechanisms may be involved in the resistance to the initiation/promotion model. As an alternative approach, a complete carcinogenesis protocol using repetitive application of DMBA alone was applied. Surprisingly, although the IL-1 alpha mice still did not develop papillomas, they did develop carcinomas de novo at an accelerated rate compared with controls. We conclude that constitutive IL-1 alpha expression rendered FVB mice completely resistant to carcinomas that required evolution from prior papillomas, but facilitated carcinomas that did not evolve from papillomas, as in the complete carcinogenesis protocol. Thus, the role of IL-1 alpha and, by extension that of other proinflammatory factors, in epithelial carcinogenesis are more complex than previously appreciated. These mice may provide a mechanism to investigate the validity of these models of human skin tumorigenesis.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.4049/jimmunol.170.11.5697 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Nonsurgical Knee Osteoarthritis Treatments for Reducing Inflammation as Measured on MRI Scans: A Systematic Review of Randomized Controlled Trials.
Orthop J Sports Med
December 2024
Orthopaedic and Arthritis Center for Outcomes Research, Department of Orthopaedic Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Background: Knee osteoarthritis (OA) is a debilitating condition, and synovitis is a structural marker of disease progression that can be identified on magnetic resonance imaging (MRI). Nonsurgical therapies have been developed with the goal of targeting this inflammation to reduce pain and slow disease progression.
Purpose: To review current randomized controlled trials (RCTs) that measured changes in pain outcomes and synovitis on MRI scans after nonsurgical treatment for persons with knee OA.
Acceleration of acute lung inflammation by IL-1α released through cell death of alveolar macrophages upon phagocytosis of fine Asian sand dust particles.
Environ Int
December 2024
Graduate School of Global Environmental Studies, Kyoto University, Kyoto, Japan; Institute for International Academic Research, Kyoto University of Advanced Science, Kyoto, Japan; Research Institute for Coexistence and Health Science, Kyoto University of Advanced Science, Kyoto, Japan.
Asian sand dust (ASD), a significant desert sand dust, contains sub-2.5 µm fine particles and adversely affects human health, particularly exacerbating respiratory diseases. Despite this, the intricate physiological responses triggered by inhaled ASD particles remain incompletely understood.
View Article and Find Full Text PDFAutoantibodies targeting interferons and GM-CSF are associated with adverse outcome risk, comorbidities, and pathogen in community-acquired pneumonia.
Front Immunol
November 2024
Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Introduction: Cytokine autoantibodies (c-aAb) have been associated with pulmonary diseases, including severe novel coronavirus disease 2019 (COVID-19) and pulmonary alveolar proteinosis. This study aimed to determine c-aAb association with community-acquired pneumonia (CAP) etiology (SARS-CoV-2, influenza, or bacteria) and c-aAb associations with CAP-related clinical outcomes and pulmonary comorbidities.
Methods: In a cohort of 665 patients hospitalized with CAP, c-aAb targeting interferon α (IFNα), IFNβ, IFNγ, interleukin-1α (IL-1α), IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured in plasma samples.
C-terminal tagging enhances the detection sensitivity of interlekin receptor type 1.
Cell Mol Biol (Noisy-le-grand)
November 2024
Department of Pathology, Nihon University School of Dentistry, Tokyo, Japan.
Substances released outside of the cells during cell necrosis are collectively called danger-associated molecular patterns (DAMPS) or alarmins. A pro-inflammatory cytokine, interleukin-1α (IL-1α) is known as a typical alarmin. IL-1α transmits signals by binding to IL-1 receptor 1 (IL-1R1), type I protein, expressed on the cell membrane of target cells, but detection of IL-1R1 at the protein and mRNA levels is difficult.
View Article and Find Full Text PDFInflammatory cytokines disrupt astrocyte exosomal HepaCAM-mediated protection against neuronal excitotoxicity in the SOD1G93A ALS model.
Sci Adv
November 2024
Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA.
Article Synopsis
- Astrocyte-secreted signals play a crucial role in neurodegenerative diseases, but the impact of proinflammatory cytokines like IL-1α, TNF-α, and C1q on these signals is not well understood.
- In our study, we discovered that these cytokines significantly reduced the secretion of astrocyte exosomes (A-Exo.) and their distribution in SOD1G93A mice, a model for amyotrophic lateral sclerosis (ALS).
- Despite A-Exo. being non-toxic to motor neurons, they provided neuroprotection against excitotoxicity, which was hindered by cytokines and SOD1G93A expression, indicating a loss-of-function mechanism in their
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!