Effects of Space Flight on Inflammasome Activation in the Brain of MiceRoy, Hadad, Rodriguez
et alCells (2025) 14 (6)
Abstract: Space flight exposes astronauts to stressors that alter the immune response, rendering them vulnerable to infections and diseases. In this study, we aimed to determine the levels of inflammasome activation in the brains of mice that were housed in the International Space Station (ISS) for 37 days. C57BL/6 mice were launched to the ISS as part of NASA's Rodent Research 1 Mission on SpaceX-4 CRS-4 Dragon cargo spacecraft from 21 September 2014 to 25 October 2014. Dissected mouse brains from that mission were analyzed by immunoblotting of inflammasome signaling proteins and Electrochemiluminescence Immunoassay (ECLIA) for inflammatory cytokine levels. Our data indicate decreased inflammasome activation in the brains of mice that were housed in the ISS for 37 days when compared to the brains of mice that were maintained on the ground, and in mice corresponding to the baseline group that were sacrificed at the time of launching of SpaceX-4. Moreover, we did not detect any significant changes in the expression levels of the pro-inflammatory cytokines TNF-α, IL-2, IFN-γ, IL-5, IL-6, IL-12p70 and IL-10 between the ground control and the flight groups. Together, these studies suggest that spaceflight results in a decrease in the levels of innate immune signaling molecules that govern inflammasome signaling in the brain of mice.
Hepatic Growth Factor as a Potential Biomarker for Lung Adenocarcinoma: A Multimodal StudySun, Yu, Zhu
et alCurr Issues Mol Biol (2025) 47 (3)
Abstract: (1) Background: Despite previous studies linking inflammatory cytokines to lung adenocarcinoma (LUAD), their causal mechanisms remain unclear. This study aims to explore the causal relationship between inflammatory cytokines and LUAD to fill this knowledge gap. (2) Methods: This study employs a comprehensive approach, integrating Mendelian randomization (MR) analysis, single-cell RNA sequencing (scRNA-seq), and transcriptomic sequencing (RNA-seq) data to investigate the relationship between inflammatory cytokines and LUAD. (3) Results: In forward MR analysis, elevated levels of hepatocyte growth factor (HGF), interleukin-1 receptor antagonist (IL-1RA), IL-5, monocyte chemoattractant protein-3, and monokine induced by interferon-γ were causally associated with an increased risk of LUAD. In reverse MR analysis, LUAD exhibited a positive causal relationship with the levels of regulated upon activation normal T cell expressed and secreted factor (RANTES) and stromal cell-derived factor-1α. The scRNA-seq data further identified specific cell populations that may influence LUAD onset and progression through the expression of particular inflammatory genes and intercellular communication. RNA-seq data analysis highlighted the role of the HGF gene in LUAD diagnosis, demonstrating its strong correlation with patient prognosis and immune cell infiltration within the tumor microenvironment. (4) Conclusions: The findings reveal a causal relationship between inflammatory cytokines and LUAD, with HGF emerging as a potential biomarker of significant clinical relevance. This study provides new insights into the molecular mechanisms underlying LUAD and lays the foundation for future therapeutic strategies.
CFTR negatively reprograms Th2 cell responses and CFTR potentiation restrains allergic airway inflammationRusznak, Thomas, Zhang
et alJCI Insight (2025)
Abstract: Type 2 inflammatory diseases are common in cystic fibrosis (CF) including asthma, sinusitis, and allergic bronchopulmonary aspergillosis. CD4+ T helper 2 (Th2) cells promote these diseases through secretion of IL-4, IL-5, and IL-13. Whether the cystic fibrosis transmembrane conductance regulator (CFTR), the mutated protein in CF, has a direct effect on Th2 development is unknown. Using murine models of CFTR deficiency and human CD4+ T cells, we show CD4+ T cells expressed Cftr transcript and CFTR protein following activation. Loss of T cell CFTR expression increased Th2 cytokine production compared to control cells. Mice with CFTR-deficient T cells developed increased allergic airway disease to Alternaria alternata extract compared to control mice. Culture of CFTR-deficient Th2 cells demonstrated increased IL-4Rα expression and increased sensitivity to IL-4 with greater induction of GATA3 and IL-13 compared to control Th2 cell cultures. The CFTR potentiator ivacaftor reduced allergic inflammation and type 2 cytokine secretion in bronchoalveolar lavage of "humanized" CFTR mice following Alternaria alternata extract challenge and decreased Th2 development in human T cell culture. Together, these data support a direct role of CFTR in regulating T cell sensitivity to IL-4 and demonstrate a potential CFTR-specific therapeutic strategy for Th2 cell-mediated allergic disease.
Serum Interleukin Levels Predict Occurrence of Acute Radiation Pneumonitis and Overall Survival in Thoracic TumoursZhang, Shen, Li
et alClin Invest Med (2025) 48 (1), 29-38
Abstract: Radiation-induced lung injury (RILI) is a significant adverse effect of thoracic radiotherapy, potentially impacting patient prognosis. The risk factors for acute radiation pneumonitis (RP) have not been fully clarified. The present study evaluated the predictive value of serum interleukins (ILs) in the occurrence of RP and overall survival in patients with thoracic cancers.This single-centre retrospective observational study enrolled 435 thoracic cancer patients who underwent chest radiation therapy. Serum levels of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, TNF-α, IFN-γ, IFN-α were measured by cytometric bead array before radiotherapy. The relationship between clinical characteristics, serum IL levels and the occurrence of RP were analyzed. Cox regression and Kaplan-Meier methods were also performed to investigate the prognostic role of serum IL levels in these patients.The incidence of RP in these patients was 17.01%. Elevated serum levels of IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, TNF-α, IFN-α were all associated with the occurrence of RP. High levels of IL-1β, IL-4, and IL-12p70 were correlated with more severe pneumonitis. Univariate and multivariate logistic regression analysis identified serum IL-6 level as an independent prognostic factor in patients receiving thoracic radiotherapy.Serum interleukin levels are linked to the development of acute RP in patients receiving thoracic radiotherapy. Serum IL-6 could serve as a valuable biomarker in identifying patients at high risk for RP, potentially guiding individualized therapeutic strategies and improving patient management in radiotherapy. Future research should focus on validating IL-6's role in larger cohorts and exploring its integration into clinical practice for the early prediction of RILI.
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