Traffic-Related PM2.5 Induces Cytosolic [Ca2+] Increase Regulated by Orai1, Alters the CaN-NFAT Signaling Pathway, and Affects IL-2 and TNF-α Cytoplasmic Levels in Jurkat T-Cells

Abstract

The atmospheric particulate matter with a diameter less than or equal to 2.5 um (PM2.5) can result in increased immune system damage or diseases, however, the possible mechanism remains unclear. In this study, we used Jurkat T cells to determine the effects of PM2.5 on T cell-mediated adaptive immune response. Our results indicated that PM2.5 exposure increased intracellular calcium ion concentration [Ca(2+)]. In contrast, cytosolic free Ca(2+) concentration [Ca(2+)]i significantly decreased in Jurkat T cells transfected with Orai1siRNA. In addition, we detected the level of interleukin (IL)-2 and tumor-necrosis factor (TNF)-α as well as other signalling molecules, including calcineurin (CaN) and NFATc2, a gene on 20q13.2 that encodes a member of the nuclear factor of activated T cells (NFAT), in the supernatant of cells exposed to PM2.5. The expression of NFATc2 protein increased in a time-dependent manner after exposure to PM2.5, but the activity of CaN decreased. NFATc2 was not consistent with IL-2 accumulation, thus indicating the involvement of other signals in the suppression of IL-2 accumulation. Our findings demonstrate that PM2.5 exposure in immune cells results in locally increased [Ca(2+)]i generated by Orai1 and CaN-NFAT gene expression, TNF-α and IL-2 cytoplasmic concentrations may be altered.

Atmospheric particulate matter2.5 promotes the migration and invasion of hepatocellular carcinoma cells

“…Therefore, PM 2.5 is likely to promote HCC development by affecting MMP13 expression, which could promote cancer invasion and migration, in addition to promoting the expression of inflammatory cytokines. This hypothesis is supported by a previous study, which revealed that PM 2.5 is associated with inflammatory cytokines as it induces TNF-α expression (30). …”

PM2.5 exposure decreases viability, migration and angiogenesis in human umbilical vein endothelial cells and human microvascular endothelial cells

“…PM2.5 also can be phagocytosed by macrophages, releasing a number of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α (12). PM2.5 exposure is capable of inducing inflammation, which is regarded as the major mechanism of PM2.5-mediated toxicity (13–15).…”

IP3R and RyR channels are involved in traffic-related PM2.5-induced disorders of calcium homeostasis

“…Moreover, PM 2.5 appeared to have more approaches to alter the [Ca 2+ ]i in T cells. Relative study has shown that PM can elicit the high [Ca 2+ ]i through the channels on cytomembrane such as Orail1 in Jurkat T cells and TRPV4 in human respiratory epithelial cells (Li et al, 2011; Tong et al, 2015). Ca 2+ is an important second messenger, it can promote critical signal transduction and functional events, such as oxidative stress (OS), apoptosis, inflammatory reaction, immune function, and other signal molecules.…”

“…Intracellular Ca 2+ channels are located in ER and SR including inositol trisphosphate receptors (IP3 R) and ryanodine receptors (RyR), which can transport Ca 2+ stored in the organelle to cytoplasm (Santulli and Marks, 2015). It was reported that traffic-related PM 2.5 can alter the conformation of Orai1 and activate the stored-operated Ca 2+ channels on the cell membrane, thus increasing extracellular Ca 2+ influx (Tong et al, 2015). A previous study has shown that diesel exhaust particles can evoke a protracted Ca 2+ influx by activation of Ca 2+ permeable transient receptor potential vanilloid family member 4 (TRPV4) ion channels in human airway epithelia (Li et al, 2011).…”