Oxidative stress

Activated iRhom2 drives prolonged PM2.5 exposure-triggered renal injury in Nrf2-defective mice (Xu et al. 2018)

In vivo and in vitro

C57BL/6 mice and HEK-293 cell and mouse podocyte

115 ± 1.5 lg/m3 for 6 h/day, 5 times/week(mice) and 0, 50, 100, and 200 lg/mL PM2.5 mass for 24 h (cell)

Long-term PM2.5 exposure causes chronic renal injury by up-regulation of iRhom2/TACE/TNF-a axis in kidney-resident macrophages

N-acetylcysteine attenuates PM-induced apoptosis by ROS-mediated Nrf2 pathway in human embryonic stem cell (Jin et al. 2019)

In vitro

Human embryonic stem cells (hESCs)

0, 1.5, 6, and 24 μg/mL of PM2.5 in corresponding media

PM2.5 present strong toxic to

hESCs, and induce cell apoptosis by ROS-mediated signaling pathway. Interestingly, NAC can decrease intracellular ROS level and protect hESCs against PM2.5-induced cell apoptosis partially through activation of the Nrf2 pathway

The Kidney Injury Induced by Short-Term PM Exposure and the Prophylactic Treatment of Essential Oils in BALB/c Mice (Zhang et al. 2018)

In vivo

BALB/c mice

Intratracheal instillation of 50 μL aqueous PM2.5 suspensions (0.5 mg PM2.5 in sterile saline) on day 0 and day 2

Short-term exposure to PM2.5 induced acute kidney damage associated with oxidative stress and inflammatory response. The activation of RAS might be the pivotal upstream of oxidative stress and inflammatory response induced by PM2.5 exposure

Inflammation

PM2.5 collected in China causes inflammatory and oxidative stress responses in macrophages through the multiple pathways (Bekki et al. 2016)

In vitro

Mouse macrophage cell line RAW264.7 and wild-type, (TLR2−/−), (TLR4−/−), (MyD88−/−) mice on a BALB/c

Exposed for 3 h to PM2.5 at the dose of 30 g/mL

Future study will be required to investigate the role of macrophages and the contribution of the endotoxin pathway and oxidative stress on the exacerbation of the Th2 immune reaction by exposure to PM2.5

Subchronic effects of inhaled ambient particulate matter on glucose homeostasis and target organ damage in a type 1 diabetic rat model (Yan et al. 2014)

In vivo

Sprague–Dawley (SD) rats (BioLasco Taiwan)

The average concentrations (mean [SD]) of PM2.5 were 13.30 [8.65]μg/m3, for 24 h/day, 7 days/week, for a total of 16 weeks (rats)

PM caused focal myocarditis, aortic medial thickness, advanced glomerulosclerosis, and accentuation of tubular damage of the kidney. PM exposure might induce the macro- and micro-vascular complications in DM through chronic hyperglycemia and systemic inflammation

iRhom2 loss alleviates renal injury in long-term PM2.5-exposed mice by suppression of inflammation and oxidative stress (Ge et al. 2018)

In vivo and in vitro

C57BL/6 mice and HEK-293 cell and mouse RAW264.7 macrophages and HK-2 and MPC5 and BMDM cells

150.1 ± 2.5 μg/m3, flow rate of 65 L/min for 6 h/day, 5 times a week (mice)

iRhom2−/− mice exhibited reduced inflammatory response, as evidenced by the reduction of interleukin 1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α) and IL-18 in kidney samples, which might be, at least partly, through inactivating TNF-α converting enzyme/TNF-α receptors (TACE/TNFRs) and inhibitor of α/nuclear factor κ B (IκBα/NF-κB) signaling pathways

Endothelial injury

PM2.5-induced oxidative stress increases adhesion molecules expression in human endothelial cells through the ERK/AKT/NF-κB dependent pathway (Rui et al. 2016)

In vitro

A human umbilical vein cell line (EA.hy926) cells

25, 50, 100, or 200 μg/mL for 1, 3, 6, 12, or 24 h

PM2.5-induced ROS may function as signaling molecules triggering ICAM-1 and VCAM-1 expressions through activating the ERK/AKT/NF-κB-dependent pathway, and further promoting monocyte adhesion to endothelial cells

Effect of Vitamin E and Omega-3 Fatty Acids on Protecting Ambient PM2.5-Induced Inflammatory Response and Oxidative Stress in Vascular Endothelial Cells (Bo et al. 2016)

In vitro

Human umbilical vein endothelial cells (HUVECs)

50 μg/mL

Inflammation and oxidative stress might be parts of the mechanisms linking PM2.5 to vascular endothelial injury

Repeat dose exposure of PM triggers the disseminated intravascular coagulation (DIC) in SD rats (Liang et al. 2019).

In vivo

Specific pathogen-free (SPF) male Sprague–Dawley (SD) rats

0, 1.8, 5.4, and 16.2 mg/kg bw every 3 days for 30 days

PM2.5 could induce inflammatory response, vascular endothelial injury, and prothrombotic state, eventually resulted in DIC

Diesel exhaust particles in the lung aggravate experimental acute renal failure (Nemmar et al. 2009).

In vivo

Male Wistar rats

0.5 or 1 mg/kg (DEP)

The presence of DEP in the lung aggravated the renal, pulmonary, and systemic effects of CP-induced ARF

IRE1alpha/XBP1s branch of UPR links HIF1alpha activation to mediate ANGII-dependent endothelial dysfunction under particulate matter (PM) 2.5 exposure (Xu et al. 2017).

In vivo and in vitro

Male Sprague–Dawley (SD) rats and human umbilical vein endothelial cells (HUVECs)

1.5 mg/kg weight, every other day for 3 times (rats) and 6.25, 12.5, and 25 μg/mL for 24 h (cell)

PM2.5 exposure instigates endoplasmic reticulum instability, leading to the induction of IRE1α/XBP1s branch of UPR and links HIF1α transactivation to mediate ANGII-dependent endothelial dysfunction

Immune response

Silica accelerated systemic autoimmune disease in lupus-prone New Zealand mixed mice (Brown et al. 2003).

In vivo

New Zealand mixed (NZM 2410) mice

30 μL saline suspensions of 1 mg crystalline silica, 2 instillations 2 weeks apart

Silica is able to exacerbate the development of autoimmune disease in a genetically susceptible mouse model. The disease acceleration involved increases in proteinuria, autoantibody levels, circulating immune complexes, immune complex deposition, and complement C3 deposition within the kidney

Silica-exposed mice generate autoantibodies to apoptotic cells (Pfau et al. 2004)

In vivo

New Zealand mixed (NZM 2410) mice

30 μL saline suspensions of 1 mg crystalline silica, 2 instillations 2 weeks apart

Silica-induced apoptosis may exacerbate autoimmune responses by exposing antigenic epitopes to the immune system

Immunoglobulin and lymphocyte responses following silica exposure in New Zealand mixed mice (Brown et al. 2004)

In vivo

New Zealand mixed (NZM 2410) mice

30 μL saline suspensions of 1 mg crystalline silica, 2 instillations 2 weeks apart

The silica-induced alterations in immunoglobulin levels, increased TNF-α, increased B1a B cells and CD4+ T cells, with decreased regulatory T cells may provide an environment that allows for increased autoreactivity

Asbestos-induced autoimmunity in C57BL/6 mice (Pfau et al. 2008)

In vivo

C57Bl/6 mice

2 doses × 60 μ g/mouse of amphibole asbestos (tremolite)

Tremolite asbestos led to the production of antinuclear antibodies, immune complex deposition in the kidneys

Apoptosis and autophagy

PM2.5 induced apoptosis in endothelial cell through the activation of the p53-bax-caspase pathway (Wang et al. 2017b)

In vitro

Human umbilical vein endothelial cells (HUVECs)

0.2, 1, 5, 25 μg/mL for 48 or 72 h

Induction of EC apoptosis is an important mechanism by which ambient PM2.5 exposure poses adverse effects on the cardiovascular system

ROS-AKT-mTOR axis mediates autophagy of human umbilical vein endothelial cells induced by cooking oil fumes-derived fine particulate matters in vitro (Ding et al. 2017)

In vitro

Human umbilical vein endothelial cells (HUVECs)

0, 25, 50, 100 μg/mL of COF-derived PM2.5, 100 μg/mL COF-derived PM2.5 + 10 mmol/L NAC, and 10 mmol/L NAC for 12, 24, and 36 h, respectively

Cooking oil fumes-derived PM2.5 (COFs-derived PM2.5) exposure can induce oxidative stress and cytotoxic effects. ROS-AKT-mTOR axis plays a critical role in HUVECs autophagy induced by COFs-derived PM2.5

Signal Transductions of BEAS-2B Cells in Response to Carcinogenic PM2.5 Exposure Based on a Microfluidic System (Zheng et al. 2017)

In vitro

BEAS-2B cells

 

The ambient fine particles could uptake into the cells by pinocytosis, mainly promoting the PI3K-Akt pathway, FGF/FGFR/MAPK/VEGF signaling, and JAK-STAT pathway

The ER stress regulator Bip mediates cadmium-induced autophagy and neuronal senescence (Wang et al. 2016)

In vitro

The rat pheochromocytoma (PC12) cell line

0, 5, 10, and 20 μM Cd for 24 h

Autophagy regulated by Bip expression after ER stress suppressed Cd-induced neuronal senescence

Arsenic and sulfur dioxide co-exposure induces renal injury via activation of the NF-kappa-B and caspase signaling pathway (Ji et al. 2019)

In vivo and in vitro

Specific pathogen-free C57BL/6 mice (4 weeks; male) and 293-T cell line (human embryonic kidney cells)

Mice of group As and As+SO2: 5 mg/L As for 60 days. Mice of group SO2 and As+SO2 5 mg/m3 SO2 for 6 h/day (from days 31 to 60) and the ratio of SO32- and HSO31- in solution is 3:1 (mM:mM). The molecular formula of arsenic is sodium arsenite (cell)

Co-exposure caused more severe diffuse sclerosing glomerulonephritis than As and SO2 exposure alone. Apoptosis was aggravated by co-exposure of As and SO2 in 293T cells. As and SO2 cause cell toxicity through increasing oxidative stress, which was increased by co-exposure

Characterization of lead, cadmium, arsenic, and nickel in PM2.5 particles in the Athens atmosphere, Greece (Thomaidis et al. 2003)

In vitro

Pb, Cd, As, and Ni in PM2.5 particles

 

It was found that Pb, As, and Ni have common sources, which could be vehicles emissions/oil combustion and resuspended road dust. Cd and a portion of As originate from industrial activities. Pb exhibited higher values during the winter period

Initial autophagic protection switches to disruption of autophagic flux by lysosomal instability during cadmium stress accrual in renal NRK-52E cells (Lee et al. 2017)

In vitro

NRK-52E cell

5, 10, 25, and 50 μM Cd2+ for a period of 0.5 h to maximally 24 h

The renal proximal tubule (PT) is the major target of cadmium (Cd2+) toxicity where Cd2+ causes stress and apoptosis

Histology technology

Effects of the ambient fine particulate matter (PM2.5) exposure on urinary metabolic profiles in rats using UPLC-Q-TOF-MS (Zhang et al. 2017)

In vivo

Male SD rats

PM2.5 suspension was injected into the trachea of rats, 2 times/week for 4 weeks

17 potential endogenous metabolites were identified from urinary samples in rats by UPLC-Q-TOF-MS

The human circulating miRNome reflects multiple organ disease risks in association with short-term exposure to traffic-related air pollution (Krauskopf et al. 2018)

In vivo

Non-smoking participants, either healthy or suffering from ischemic heart disease (IHD) or chronic obstructive pulmonary disease (COPD)

Participants walked about 6 km/2 h (an exposure period), personal ambient air pollution levels of PM were assessed using a real-time condensation particle counter

54 circulating miRNAs to be dose- and pollutant species-dependently associated with PM2.5 already after 2 h of exposure. These circulating miRNAs actually reflect the adverse consequences of traffic pollution-induced toxicity in target tissues including the lung, heart, kidney, and brain