Organic UV Filters Induce Toll-like-Receptors and Related Signaling Pathways in Peripheral Blood Mononuclear Cells of Juvenile Loggerhead Sea Turtles (Caretta caretta)

Abstract

Recent evidence suggests that exposure to organic ultraviolet filters (UV filters) is associated with dysregulated neuroendocrine-immune homeostasis. Marine species are likely to be among the most vulnerable to UV filters due to widespread diffusion of these chemicals in the aquatic environment. In the present study, the effects of UV filter bioaccumulation on toll-like-receptors (TLRs) and related signaling pathways were investigated in peripheral blood mononuclear cells (PBMCs) of juvenile loggerhead sea turtles (Caretta caretta). We found that the expression of both TLR1 and TLR2 was significantly increased in UV-filter exposed turtles compared to control animals. Similarly, the signaling pathway downstream of activated TLRs (i.e., Ras-related C3 botulinum toxin substrate 1 (RAC1), Phosphoinositide 3-kinase (PI3K), serine/threonine-protein kinase (AKT3), and nuclear factor κB (NF-κB)) was significantly up-regulated, leading to an enhanced transcription of pro-inflammatory cytokines. In addition, we demonstrated that high levels of plasma UV filters increased lipid peroxidation in sea turtles' PBMCs. Our results indicated that UV filters affected the inflammatory responses of PBMCs via modulation of the TLR/NF-κB signaling pathway and provided a new insight into the link between exposure to sunscreen agents and sea turtle health.

Keywords: UV filters; endocrine disruptors; immunotoxicity; loggerhead sea turtles; pro-inflammatory cytokines; toll-like receptors.

Figure 1

Size distribution of the two groups of loggerhead turtles analyzed in this study. Values are given as mean + SD. Dot line shows CCL threshold for identifying immature specimens [26,27,30].

Figure 2

Illustration of the TLR/NF-κB signaling pathway, along with the log2 fold changes of 11 pathway genes in UV filter exposed loggerheads (LOQpos). Interleukin 1 beta (IL-1β) gene expression dataset was collected from our previous work, Cocci et al. [8]. ROS: reactive oxygen species; DAMPs: damage-associated molecular patterns; LPO: lipid peroxidation.

Figure 3

Mean mRNA fold change (+SD) of toll-like-receptors (TLRs) 1 and 2, Ras-related C3 botulinum toxin substrate 1 (RAC1), Phosphoinositide 3-kinase (PI3K), serine/threonine-protein kinase (AKT3), nuclear factor κB (NF-κB), inhibitory protein kappa B alpha (IkBα), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and IL-12 relative to LODneg group (adjusted average LODneg value is 1) is shown. **, p ≤ 0.01; **** p ≤ 0.0001 (unpaired t-tests).

Figure 4

Effects of UV filters on lipid peroxidation (LPO) in loggerhead peripheral blood mononuclear cells. Results are expressed as percentage (%) of mean + SD versus LODneg group. * p ≤ 0.05 (unpaired t-tests).