Nanoplastics activate a TLR4/p38-mediated pro-inflammatory response in human intestinal and mouse microglia cells

© 2023 The Authors. Published by Elsevier B.V. ; The crescent presence of nanoplastics in the environment raises concerns regarding their potential impact on health. This study exposed human colon adenocarcinoma cells (HT29) and microglia cells (N9) to nanoplastics (25 nm, 50 nm, and 100 nm Polystyrene) to investigate their inflammatory responses, which are vital for body's defence. Although cytotoxicity remained generally low, HT29 cells exhibited a notable upregulation of p50 and p38 expression, concomitant with elevated TLR4 expression, in contrast with N9 cells that showed a less pronounced upregulation of these proteins. Additionally, nanoplastic exposure increased IL-1ß levels, partially attenuated by pre-exposure to TLR4 or p38 inhibitors. Intriguingly, N9 cells exposed to nanoplastics exhibited substantial increases in iNOS mRNA. This effect was entirely prevented by pre-exposure to TLR4 or p38 inhibitors, while TNF-α mRNA levels remained relatively stable. These findings underscore the potential of nanoplastics to activate inflammatory pathways, with response kinetics varying depending on the cell type. ; This research was supported by Fundação para a Ciência e Tecnologia, I.P, through: the Ph.D grant (SFRH/BD/144333/2019), JA; Norma Transitória - DL57/2016/CP1376/CT002, VB; through the Scientific Employment Stimulus - Institutional Call (CEECINST/00102/2018), MM; Nanoplastox Project – Nanoplastic Toxicity: from gut inflammation to systemic effects (2022.04884. PTDC); PAHMIX project - Mixtures of Environmental Carcinogens: a molecular approach to improve environmental risk assessment strategies (PTDC/CTA-AMB/29173/2017); MARE - Marine and Environmental Sciences Centre Strategic Project (UIDB/04292/2020), Associate Laboratory ARNET (LA/P/0069/2020) and iMed. ULisboa’s Strategic Project (UID/DTP/04138/2020). The authors acknowledge Isabella Bramatti, Beatriz Matos and Neusa Figueiredo from the Marine and Environmental Sciences Centre and Carolina Carola Alfenim from University of Lisbon for their ...