EFFECTS OF FIBROGENIC AND NON FIBROGENIC NANOMATERIALS ON CELLULAR AND MOLECULAR RESPONSES IN THP-1 MACROPHAGE

Traditional toxicological testing of nanomaterials is often low-throughput and time-consuming. Here, we aimed to develop an economically viable in vitro assay to prescreen nanomaterials with fibrogenic potential. To this end, we tested the generation of reactive oxygen species (ROS) as well as cytokines (pro- and anti-inflammatory) by macrophages following treatment with fibrogenic and non-fibrogenic nanomaterials. Both classes of nanomaterials induced ROS indistinguishably, suggesting that ROS production doesn’t predict nanomaterial fibrogenicity. We observed higher levels of IL1β and IL6 in macrophages treated with fibrogenic nanomaterials. Analysis of single-cell RNA-Sequencing data of fibrotic lungs from rodents and humans revealed overexpression of Brain Abundant membrane attached signal protein 1 and Plexin D1 in alveolar macrophages. Notably, BASP1 exhibited overexpression in macrophages when subjected to fibrogenic NPs, a response not observed with non-fibrogenic NPs. This high-throughput in-vitro assay leveraging the expression of BASP1 could potentially help in prescreening toxic nanomaterials with fibrogenic potential.