ABSTRACT
BACKGROUND: Individuals with certain chronic inflammatory lung diseases have a higher risk of developing lung cancer (LC). However, the underlying mechanisms remain largely unknown. Here, we hypothesized that chronic exposure to house dust mites (HDM), a common indoor aeroallergen associated with the development of asthma, accelerates LC development through the induction of chronic lung inflammation (CLI). METHODS: The effects of HDM and heat-inactivated HDM (HI-HDM) extracts were evaluated in two preclinical mouse models of LC (a chemically-induced model using the carcinogen urethane and a genetically-driven model with oncogenic KrasG12D activation in lung epithelial cells) and on murine macrophages in vitro. Pharmacological blockade or genetic deletion of the Nod-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, caspase-1, interleukin-1ß (IL-1ß), and C-C motif chemokine ligand 2 (CCL2) or treatment with an inhaled corticosteroid (ICS) was used to uncover the pro-tumorigenic effect of HDM. RESULTS: Chronic intranasal (i.n) instillation of HDM accelerated LC development in the two mouse models. Mechanistically, HDM caused a particular subtype of CLI, in which the NLRP3/IL-1ß signaling pathway is chronically activated in macrophages, and made the lung microenvironment conducive to tumor development. The tumor-promoting effect of HDM was significantly decreased by heat treatment of the HDM extract and was inhibited by NLRP3, IL-1ß, and CCL2 neutralization, or ICS treatment. CONCLUSIONS: Collectively, these data indicate that long-term exposure to HDM can accelerate lung tumorigenesis in susceptible hosts (e.g., mice and potentially humans exposed to lung carcinogens or genetically predisposed to develop LC).
Subject(s)
Asthma , Lung Neoplasms , Humans , Animals , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pyroglyphidae , Lung/pathology , Asthma/metabolism , Asthma/pathology , Lung Neoplasms/chemically induced , Lung Neoplasms/metabolism , Disease Models, Animal , Tumor MicroenvironmentABSTRACT
National School Lunch Program (NSLP) standards recently changed significantly. The Healthy, Hunger-Free Kids Act (HHFKA) presumably improved the dietary quality (DQ) of meals, whereas Child Nutrition Program (CNP) Flexibilities appear to decrease DQ. This variability has not been quantified. Our objective was to determine differences in DQ between elementary school lunch menus meeting NSLP standards: School Meal Initiative (SMI), HHFKA, CNP Flexibilities, and evidence-based best practices (BP). A base menu was portioned per NSLP standards and analyzed for nutrient content and DQ. Statistical analyses included 1-factor ANOVA, Kruskal-Wallis, and Dunnett's test. The BP menu had higher whole fruit and whole grain Healthy Eating Index scores than SMI (Ps < 0.0083). The BP and HHFKA menus had higher refined grain and added sugars scores than SMI (Ps < 0.0083). The SMI menu had lower total vegetable and saturated fat scores than all menus (Ps < 0.0083). This study informs policy toward improving standards, positively affecting child health and academic performance through higher-DQ lunches.
