ABSTRACT
Triphenyl phosphate (TPHP) is one of the most widely used organic phosphorus flame retardants and is ubiquitous in the environment. Studies have been reported that TPHP may lead to obesity, neurotoxicity and reproductive toxicity, but its impact on the immune system is almost blank. The present study was aimed to investigate the potential immunotoxicity of TPHP on macrophages and its underlying mechanism. The results demonstrated for the first time that TPHP (12.5, 25, and 50 µM)-induced F4/80+ CD11c+ phenotype of RAW 264.7 macrophages, accompanied by increased mRNA levels of inflammatory mediators, antigen-presenting genes (Cd80, Cd86, and H2-Aa), and significantly enhanced the phagocytosis of macrophage. Meanwhile, TPHP increased the expression of Toll-like receptor 4 (TLR4), and its co-receptor CD14, leading to significant activation of the downstream ERK/NF-κB pathway. However, co-exposure of cells to TAK-242, a TLR4 inhibitor, suppressed TPHP-induced F4/80+ CD11c+ phenotype, and down-regulated inflammatory mediators and antigen-presentation related genes, via blocked the TLR4/ERK/NF-κB pathway. Taken together, our results suggested that TPHP could induce macrophage dysfunction through activating TLR4-mediated ERK/NF-κB signaling pathway, and it may be the potential reason for health-threatening consequences.
Subject(s)
NF-kappa B , Toll-Like Receptor 4 , NF-kappa B/metabolism , Toll-Like Receptor 4/genetics , Toll-Like Receptor 4/metabolism , Macrophages , Inflammation Mediators/metabolismABSTRACT
PURPOSE: To examine the association of sleep duration and quality in early pregnancy with gestational diabetes mellitus (GDM), and explore their interaction effect on GDM. METHODS: Participants from 2 hospitals were enrolled in this case-control study between April 2018 and November 2020. Sleep duration and quality were measured using the Pittsburg Sleep Quality Index (PSQI). RESULTS: A total of 1300 participants (396 GDM and 904 controls) were included. After adjusting for potential confounders, higher global PSQI scores or poor sleep quality were associated with GDM with odds ratios of 1.13 (95% CI 1.07, 1.19, p < 0.001) and 1.75 (95% CI 1.29, 2.38, p < 0.001), respectively; sleep duration < 7 h, 9-9.9 h and ≥ 10 h were all associated with increased GDM with odds ratios of 4.28 (95% CI 2.51, 7.31, p < 0.001), 1.69 (95% CI 1.20, 2.39, p = 0.003), and 4.42 (95% CI 3.01, 6.50, p < 0.001), respectively. In the stratified analysis based on sleep duration, the effect of poor sleep quality on GDM in the < 7 h group (OR 5.47, 95% CI 2.57, 11.64, p < 0.001) was much stronger than that in the 7-8.9 h group (OR 1.24, 95% CI 0.81, 1.91, p = 0.327), and the p value of the interaction was 0.011. CONCLUSIONS: Poor sleep quality and short or long sleep duration in early pregnancy were all associated with GDM, and an interaction effect between short sleep duration and poor sleep quality on GDM was noted.
