UC San Diego

Previous investigations in the laboratory demonstrated that chronic exposure to house dust mites (HDM), a common indoor aeroallergen associated with the development of asthma, accelerates lung cancer (LC) development in mice. The tumor-promoting effect of HDM was mainly due to NLRP3 inflammasome activation in macrophages and increased IL-1β production as the blockade of these molecules abrogated the effect of HDM on tumor development. Interestingly, the lung tumor-promoting effect of HDM was not completely abolished by heat treatment of the HDM extract, suggesting that the heat-insensitive factors play a role in its pro-tumorigenic effect. Chitin, a component of the HDM exoskeleton, is an abundant 1,4-beta blinked N-glucosamine polymer that is rigid and hard to degrade. Here we performed additional mechanistic studies using the RAW 264.7 mouse macrophage cell line and bone marrow-derived macrophages (BMDMs), and investigated the specific effect of chitin, a major constituent of HDM, on IL-1β production. We also test the effect of chronic exposure to chitin on LC development in a genetically engineered mouse model (GEMM) of mutated KRAS.