Nanoplastic and microplastic exposure induces epidermal barrier dysfunction and initiates keratinocyte inflammation

Summary: Abstract Body: Skin is our most extensive interface with the environment. At this frontier, the epidermal barrier protects us from myriad environmental exposure agents. Among these are nanoplastics and microplastics (NPs/MPs), a relatively recent class of agents found globally in the environment and within organisms. We are continuously exposed to NPs/MPs through contact with the air, water, personal and household care items, and textiles. Yet, despite their prevalence and constant contact with the body, the potential toxic effects of NPs/MPs on the epidermal barrier and skin immune homeostasis is unknown. As such, we sought to identify the effects of a common NP/MP, polystyrene (PS), on barrier function and cytokine expression in epidermis organoids engineered from primary keratinocytes (N=3). Daily topical exposure (4 h) to PS-NPs/MPs (100 nm, 1.1 µm, 3 µm) for 7 days induced a >40% reduction (p<0.04) in barrier function measured by TEER at all sizes and doses (1, 10, 100 ppm). These effects were not due to cytotoxicity as constant exposure up to 120 h did not change the growth of keratinocytes in 2D or affect cellular morphology (N=3), despite observing internalized PS. Next, we measured the transcripts of barrier components in organoids chronically exposed to PS. There was a loss (p<0.01) in expression of barrier envelope components FLG and LOR and CLDN4 of tight junctions. Agents that damage the barrier often initiate inflammation and cytokine release in keratinocytes, further impairing barrier function. We find heightened (p<0.05) transcripts of key inflammatory mediators and known barrier disruptors TNF, IL1β, IFNγ, and IL6 in organoids. Taken together, our new data show that PS-NPs/MPs induce epidermal barrier damage and cytokine production in keratinocytes, indicating that NPs/MPs alter skin function and provoke inflammation. As MPs/NPs are pervasive in the environment with levels that will only continue to increase, understanding the consequence of skin exposure is imperative to our comprehension of how these environmental exposure agents affect humans. Xa Nguyen¹, E Cassidy¹, Ng Bozbas¹, A Patel¹, T Boddupalli¹, D Barzallo¹, K Russell¹, B Perez White¹ 1. Northwestern U, Chicago, IL, United States. Epidermal Structure and Barrier Function