Search

Black carbon (BC) correlates with the occurrence and progression of atherosclerosis and other cardiovascular diseases. Increasing evidence has demonstrated that BC could impair vascular endothelial cells, but the underlying mechanisms remain obscure. It is known that IL‐33 exerts a significant biological role in cardiovascular disease, but little is known about the molecular regulation of IL‐33 expression at present. We first found that BC significantly increased IL‐33 mRNA in EA.hy926 cells in a concentration and time‐dependent manner, and we conducted this study to explore its underlying mechanism. We identified that BC induced mitochondrial damage and suppressed autophagy function in EA.hy926 cells, as evidenced by elevation of the aspartate aminotransferase (GOT2), reactive oxygen species (ROS) and p62, and the reduction of mitochondrial membrane potential (ΔΨm). However, ROS cannot induce IL‐33 mRNA‐production in BC‐exposed EA.hy926 cells. Further, experiments revealed that BC could promote IL‐33 mRNA production through the PI3K/Akt/AP‐1 and p38/AP‐1 signaling pathways. It is concluded that BC could induce oxidative stress and suppress autophagy function in endothelial cells. This study also provided evidence that the pro‐cardiovascular‐diseases properties of BC may be due to its ability to stimulate the PI3K/AKT/AP‐1 and p38/AP‐1 pathway, further activate IL‐33 and ultimately result in a local vascular inflammation. [ABSTRACT FROM AUTHOR]

Black carbon (BC) can combine with organic matter and form secondary pollutants known as aged BC. BC and aged BC can cause respiratory system inflammation and induce lesions at relevant sites, but the underlying mechanism has remained unknown. To gain insight into the potential mechanisms, we focused on macrophages and transforming growth factor β-activated kinase 1 (TAK1) which are a crucial factor in inflammation. Our research aims to determine the role of TAK1 in macrophages in pulmonary inflammation induced by particulate matter. In this study, BC and 1,4-naphthoquinone were mixed to model aged BC (1,4NQ-BC) in atmosphere. BC induced mice lung inflammation model, lung macrophage knock-down TAK1 animal model and primary macrophage knock-down TAK1 model were used to explore whether TAK1 in macrophage is a critical role in the process of inflammation. The results showed that the expressions of inflammatory cytokines (IL-1β, IL-6, IL-33) mRNA were significantly increased and the phosphorylation of MAPK and NF-κB signaling pathway related proteins were enhanced in RAW 264.7 cell lines. In vivo studies revealed that the indicators of pulmonary inflammation (pathology, inflammatory cell numbers) and related cytokines (IL-1β, IL-6, IL-33) mRNA expressions in CD11c-Map3k7−/− animals were significantly lower than wild-type animals after mice were instilled particles. In mice primary macrophages, the expressions of IL-6, IL-33 mRNA were inhibited after TAK1 gene was knock-down. These results unequivocally demonstrated that TAK1 plays a crucial role in BC induced lung inflammation in mice, and we can infer that BC and 1,4NQ-BC cause these inflammatory responses by stimulating pulmonary macrophages. • BC has different physico-chemical properties compared with 1,4NQ-BC. • TAK1 knock-down in macrophages could alleviate mice lung inflammation induced by BC and 1,4NQ-BC. • TAK1 plays a key role in the production of IL-33 by macrophages. [ABSTRACT FROM AUTHOR]

The impacts of environmental PM 2.5 on public health have become a major concern all over the world. Many studies have shown that PM 2.5 still poses a threat to public health even at very low levels. Physical or chemical reactions occur between primary particles and other components in the environment, which changes the properties of primary particles. Such newly formed particles with changed properties are called secondary particles. Ozone-oxidized black carbon (oBC) is a key part of PM 2.5 and a representative secondary particle. Macrophages extracellular traps (METs) is a means for macrophages to capture and destroy invading pathogens, thereby exercising innate immunity. Necroptosis is a kind of programmed cell death, which is accompanied by the destruction of membrane integrity, thus inducing inflammatory reaction. However, there is no research on the crosstalk mechanism between necroptosis and MET after oBC exposure. In our study, AO/EB staining, SYTOX Green staining, fluorescent probe, qPCR, Western blot, and immunofluorescence were applied. This experiment found that under normal physiological conditions, when macrophages receive external stimuli (such as pathogens; in our experiment: phorbol 12-myristate 13-acetate (PMA)), they will form METs, capture and kill pathogens, thus exerting innate immune function. However, exposure to oBC can cause necroptosis in macrophages, accompanied by increased levels of reactive oxygen species (ROS) and cytosolic calcium ions, as well as the expression disorder of inflammatory factors and chemokines, and prevent the formation of METs, lose the function of capturing and killing pathogens, and weaken the innate immune function. Notably, inhibition of necroptosis restored the formation of METs, indicating that necroptosis inhibited the formation of METs. This study was the first to explore the crosstalk mechanism between necroptosis and METs after oBC exposure. [Display omitted] • Ozone-oxidized black carbon (oBC) is a form of simulating the aging of BC in nature. • oBC can cause necroptosis in macrophages. • oBC can prevent the formation of macrophage extracellular traps (METs). • Necroptosis inhibited the formation of METs, and the two can interconvert. • Crosstalk mechanism between necroptosis and METs was explore for the first time after oBC exposure. [ABSTRACT FROM AUTHOR]

Black carbon (BC) is an important component of atmospheric PM 2.5 and the second largest contributor to global warming. 1,4-naphthoquinone-coated BC (1,4 NQ-BC) is a secondary particle with great research value, so we chose 1,4 NQ-BC as the research object. In our study, mitochondria and lysosomes were selected as targets to confirm whether they were impaired by 1,4 NQ-BC, label free proteomics technology, fluorescent probes, qRT-PCR and western blots were used to investigate the mechanism of 1,4 NQ-BC toxicity. We found 494 differentially expressed proteins (DEPs) in mitochondria and 86 DEPs in lysosomes using a proteomics analysis of THP1 cells after 1,4 NQ-BC exposure for 24 h. Through proteomics analysis and related experiments, we found that 1,4 NQ-BC can damage THP-1-M cells by obstructing autophagy, increasing lysosomal membrane permeability, disturbing the balance of ROS, and reducing the mitochondrial membrane potential. It is worth noting that 1,4 NQ-BC prevented the removal of FTL by inhibiting autophagy, and increased IL-33 level by POR/FTL/IL-33 axis. We first applied proteomics to study the damage mechanism of 1,4 NQ-BC on THP1 cells. Our research will enrich knowledge of the mechanism by which 1,4 NQ-BC damages human macrophages and identify important therapeutic targets and adverse outcome pathways for 1,4 NQ-BC-induced damage. [Display omitted] • PM 2.5 is a mixture, and 1,4 NQ-BC is a major component of PM 2.5. • 1,4 NQ-BC is a form of simulating the aging of BC in nature, which is more realistic. • We first applied proteomics to study the damage mechanism of 1,4 NQ-BC on THP1 cells. • 1,4 NQ-BC prevented the removal of FTL by inhibiting autophagy. • 1,4 NQ-BC increased IL-33 level by POR/FTL/IL-33 axis. [ABSTRACT FROM AUTHOR]

Black carbon (BC) reacts with different substances to form secondary pollutants called aged black carbon, which causes inflammation and lung damage. BC and aged BC may enhance IL-33 in vivo, which may be derived from macrophages. The pro-inflammatory effect of IL-33 makes it essential to determine the source of IL-33, so it guides us to explore how to alleviate lung injury. In this study, a human bronchial epithelial cell line of 16HBE cells was selected, and aged BC (1,4-NQ coated BC and ozone oxidized BC) was used. We found that both BC and aged BC were able to up-regulate the mRNA expression of IL-1β, IL-6, and IL-8 except IL-33. However, the Mitogen-activated protein kinases (MAPKs) and Phosphatidylinositol 3-kinase (PI3K)/Protein kinase B (AKTs) pathways remained inactive. After pretreatment with Lipopolysaccharide (LPS), IL-33 mRNA expression was significantly increased in 16HBE cells and MAPKs and PI3K/AKT were activated. These results suggested that MAPKs and PI3K/AKT pathways were involved in the elevation of IL-33. Furthermore, epithelial cells are unlikely to be the source of lung inflammation caused by elevated IL-33 in BC and aged BC. Image 1 • Black carbon and aged black carbon induce inflammatory effects in human bronchial epithelial cells. • BC and aged BC-induced IL-33 in HBE cells might only be up-regulated following stimuli, like LPS challenge. • MAPKs and PI3K/AKTs get involved in the elevation of IL-33 in LPS-pretreated HBE cells. • BC and aged BC increase IL-1β, IL-6 and IL-33 not via MAPKs or PI3K/AKTs. • Epithelial cells may not be the source of IL-33 elevated in BC and aged BC-induced inflammation. [ABSTRACT FROM AUTHOR]

PM2.5 still poses a threat to public health even at very low levels. Black carbon (BC) is a key component of PM2.5. Macrophage extracellular traps (METs) are a means by which macrophages capture and destroy invading pathogens. Necroptosis is an inflammatory programmed cell death. However, there is no research on the crosstalk mechanism between necroptosis and METs after BC exposure. In our study, fluorescence labeling, fluorescent probes, qPCR, and immunofluorescence were applied. Our research found that under normal physiological conditions, when macrophages receive external stimuli (in our experiment, phorbol 12-myristate 13-acetate (PMA)), they will form METs, thus exhibiting innate immune function. However, exposure to BC can cause necroptosis in macrophages accompanied by increased levels of ROS and cytosolic calcium ions as well as altered expression of inflammatory factors and chemokines that prevent the formation of METs, and weakening innate immune function. Notably, inhibition of necroptosis restored the formation of METs, indicating that necroptosis inhibits the formation of METs. Our experiment will enrich the understanding of the mechanism of macrophage injury caused by BC exposure, provide a new direction for studying harmful atmospheric particle toxicity, and propose new therapeutic insights for diseases caused by atmospheric particulate matter. This study is the first to explore the crosstalk mechanism between necroptosis and METs after BC exposure. [Display omitted] • Black carbon (BC) can cause necroptosis in macrophages. • BC can prevent the formation of macrophage extracellular traps (METs). • BC induced necroptosis inhibits the formation of METs. • Necroptosis and METs could interconvert. • This study is the first to investigate the crosstalk mechanism between necroptosis and METs after BC exposure. [ABSTRACT FROM AUTHOR]

Black carbon (BC) is a key component of atmospheric particles and has a significant effect on human health. Oxidation could change the characteristics of BC and increase its toxicity. The comparison of lung damage in mice exposed to BC and ozone-oxidized BC (oBC) particles is investigated in this study. Mice which were intratracheally instilled with particles have a higher expression of IL-1β, IL-6 and IL-33 in bronchoalveolar lavage fluid (BALF). Also, the IL-6, IL-33 mRNA expression in the lung tissue of mice instilled with oBC was higher than that of mice instilled with BC. The expression of CD3 in the lung tissue of mice intratracheally instilled with oBC was higher than the mice distilled with BC. The pathology results showed that the lung tissue of mice instilled with oBC particles have much more inflammatory cells infiltration than that of mice treated with BC. It is believed that the PI3K-AKT pathway might be involved in the oBC particles caused lung damage. Results indicated that oBC particles in the atmosphere may cause more damage to health. [ABSTRACT FROM AUTHOR]