Search

Some studies show that Cd(2+) and Hg(2+) may induce cell proliferation and apoptosis via biphasic dose-response relationship in human cells. However, mechanisms underlying this phenomenon are still in puzzle. In this study, we aim at detecting the biphasic effects of Cd(2+) and Hg(2+) on proliferation and apoptosis of human embryonic kidney 293 (HEK293) cells, analyzing the change of the mitogen-activated protein kinase (MAPK) pathways, and discussing the relationship between them. The results demonstrate that Cd(2+) and Hg(2+) can stimulate cell proliferation at lower concentrations (0.05 and 0.5 microM) but inhibit it at higher concentrations (50 and 500 microM). Apoptosis increases at higher concentrations (50 and 500 microM) of Cd(2+) and Hg(2+). While 0.5 microM Cd(2+) and Hg(2+) decrease the JNK phosphorylation, 50 microM Cd(2+) and Hg(2+) increase the JNK and P38 phosphorylation. When HEK293 cells are treated with 20 microM JNK inhibitor or 100 microM ERK1/2 inhibitor, the cell proliferation do not increase significantly at low concentrations (0.05 and 0.5 microM), but still decrease at high concentrations (50 and 500 microM). When HEK293 cells are treated with 20 microM P38 inhibitor, the tendency of cell proliferation is not affected. Data in our study suggests that activation of MAPK pathway may be involved in the biphasic effect induced by Cd(2+) and Hg(2+).

Background: Air pollution increases the morbidity and mortality of cardiovascular disease (CVD). Atherosclerosis (AS) is the pathological basis of most CVD, and the progression of atherosclerosis and the increase of fragile plaque rupture are the mechanism basis of the relationship between atmospheric particulate pollution and CVD. The aim of the present study was to investigate the effects of coal-fired fine particulate matter (PM2.5) on the expression levels of atherosclerosis-related proteins (von Willebrand factor (vWF), Endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin, and to explore the role and mechanism of the progression of atherosclerosis induced by coal-fired PM2.5 via the mitogen-activated protein kinase (MAPK) signaling pathways. Methods: Different concentrations of PM2.5 were given to apolipoprotein-E knockout (ApoE−/−) mice via intratracheal instillation for 8 weeks. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of vWF, ET-1 in serum of mice. Immunohistochemistry was used to observe the expression and distribution of ICAM-1 and E-selectin in the aorta of mice. Western blot was used to investigate the phosphoylation of proteins relevant to MAPK signaling pathways. Results: Coal-fired PM2.5 exacerbated atherosclerosis induced by a high-fat diet. Fibrous cap formation, foam cells accumulation, and atherosclerotic lesions were observed in the aortas of PM2.5-treated mice. Coal-fired PM2.5 increased the protein levels of ET-1, ICAM-1, and E-selectin, but there was no significant difference in the vWF levels between the PM2.5-treatment mice and the HFD control mice. Coal-fired PM2.5 promoted the phosphorylation of p38, c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) in aortic tissues of mice. Conclusion: Coal-derived PM2.5 exacerbated the formation of atherosclerosis in mice, increased the expression levels of atherosclerosis-related proteins in mice serum, and promoted the phosphorylation of proteins relevant to MAPK signaling pathway. Thus, MAPK signaling pathway may play a role in the atherosclerosis pathogenesis induced by Coal-derived PM2.5. [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]

Black carbon (BC) is a product of incomplete combustion of fossil fuels and vegetation. The compelling evidence has demonstrated that it has a close relationship with several respiratory and cardiovascular diseases. BC provides the reactive sites and surfaces to absorb various chemicals, such as polycyclic aromatic hydrocarbons (PAH). Naphthoquinone is a typical PAHs which was found in particulate matter (PM) and 1,4NQ-BC owned high oxidative potential and cytotoxicity. IL-33 is an alarmin which increases innate immunity through Th2 responses. It was reported that IL-33 was a potent inducer of pro-inflammatory cytokines, like IL-6. In our previous study, it was revealed that 1,4NQ-BC instilled intratracheally to mice could trigger the lung inflammation and stimulate the secretion of IL-33 in lung tissue. We found that IL-33 could induce inflammation in lung itself. When the macrophages were eliminated, the secretion of IL-33 was reduced and the pathological damage in the lung was relieved after exposure to 1,4NQ-BC. Both MAPK and PI3K/AKT signal pathways were involved in the process of IL-33 secretion and the lung inflammation induced by 1,4NQ-BC. The findings herein support the notion that after exposure to 1,4NQ-BC, the increased secretion of IL-33 was mainly derived from macrophages through both MAPK and PI3K/AKT signal pathways. Image 1 • IL-33 can induce lung inflammation itself. • IL-33 plays a key role in the progress which 1,4NQ-BC triggered lung inflammation. • IL-33 may derive from macrophages after 1,4NQ-BC treatment. • MAPK and PI3K/AKT pathways are involved in the lung inflammation not only mediated by IL-33, but also 1,4NQ-BC. [ABSTRACT FROM AUTHOR]

Abstract Black carbon (BC) is a key component of atmospheric particles which has adverse effects on human health. Oxidation could lead to chemical property and toxicity potency changes of BC. The key cytokines participating in lung damage in mice induced by BC and ozone-oxidized BC (oBC) particles have been investigated in this study. It was concluded that oBC has stronger potency of inducing lung damage in mice comparing to BC. IL-6 and IL-33 were hypothesized to play important roles in this damage. Accordingly, IL-6 and IL-33 neutralizing antibodies were used to explore which cytokine might play a key role in lung inflammation induced by BC and oBC. As a result, IL-6 neutralizing antibody did not alleviate the lung damage induced by BC and oBC. However, IL-33 neutralizing antibody prevented BC and oBC induced lung damage. Furthermore, IL-33 neutralizing antibody treatment reduced IL-6 mRNA expression. It is hypothesized that MAPK and PI3K-AKT pathways might be involved in the oBC particles caused lung damage. It was concluded that IL-33 plays a key role in BC and oBC induced lung damage in mice. Graphical abstract Unlabelled Image Highlights • oBC has stronger potency in inducing lung inflammation in mice than BC. • IL-33 neutralizing antibody prevented BC and oBC induced lung damage. • IL-33 neutralizing antibody prevented BC and oBC induced lung damage through MAPK and PI3K/AKT pathways. [ABSTRACT FROM AUTHOR]

Grape-seed proanthocyanidins (GSPs) have been shown to function as an anti-oxidant and anti-inflammatory agent with little toxicity in vivo and in vitro. However, little is known about their anti-inflammatory properties and mechanisms of action. The specific focus being its effects on the MAP kinases and nuclear factor-kappaB (NF-κB) signal transduction pathways in lipopolysaccharide (LPS) -stimulated RAW264.7 cells. GSPs extract has been found to suppress the mRNA expression of pro-inflammatory cytokines like tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and inflammatory molecule of cyclooxygenase-2 (COX-2) while mRNA level of IL-10 was greatly promoted. Furthermore, GSPs extract inhibited the expression of phosphorylated ERK, JNK and P38, as well as phosphorylated IKKα/β and NF-κB p65 subunit. In conclusion, our results show that GSPs extract showed its anti-inflammatory and immunomodulatory properties by suppressing the activation of MAP kinases and NF-κB signal transduction pathways. [ABSTRACT FROM AUTHOR]

Highlights: [•] MAP4K4 is required for the proliferation and activation of CD4+ T cells. [•] MAP4K4 deletion in CD4+ T cells suppresses the IL-2 and IFN-γ production. [•] MAP4K4 is essential for promoting the development of CD25+ CD4+ Tregs. [•] MAP4K4 deficiency prevents the phosphorylation of Erk, Jnk, p38 and PKC-θ. [ABSTRACT FROM AUTHOR]