Fine Particulate Matter and Sulfur Dioxide Coexposures Induce Rat Lung Pathological Injury and Inflammatory Responses Via TLR4/p38/NF-κB Pathway

Abstract

Fine particulate matter (PM) and sulfur dioxide (SO) are 2 common air pollutants, but their toxicological effects of coexposure are still not fully clear. In this study, SO exposure (5.6 mg/m) couldn't cause obvious inflammatory responses in rat lungs. The PM exposure (1.5 mg/kg body weight) increased inflammatory cell counts in bronchoalveolar lavage fluid (BALF) and some inflammation damage. Importantly, SO and PM (1.5, 6.0, and 24.0 mg/kg) coexposure induced pathological and ultrastructural damage and raised inflammatory cells in BALF compared with the control. Also, they significantly elevated the levels of pro-inflammatory cytokines, adhesion molecule, and nitric oxide (NO) and promoted the gene expression of nuclear factor kappa B (NF-κB), phosphorylated p38 (p-p38), and Toll-like receptor 4 (TLR4) in rat lungs treated with higher dose of PM (6.0 and 24.0 mg/kg) plus SO relative to the control or SO group, along with the decreased inhibitor of NF-κBα and increased inhibitor of NF-κB kinase β expressions. The changes in the inflammatory markers in the presence of PM plus SO were not significant compared with the PM group. The results indicated that inflammatory injury and pathological and ultrastructural damage in rat lungs exposed to PM plus SO were involved in TLR4/p38/NF-κB pathway activation accompanied by oversecretion of pro-inflammatory cytokine, adhesion molecule, and NO. It provides more useful evidence to understand the possible toxicological mechanism that PM and SO copollution exacerbate lung disease.

Autophagy Induced FHL2 Upregulation Promotes IL-6 Production by Activating the NF-κB Pathway in Mouse Aortic Endothelial Cells after Exposure to PM2.5

“…PM2.5 regulates inflammatory responses by activating multiple signaling pathways. Inflammatory injury in rat lungs exposed to PM2.5 and SO 2 is associated with p38/NF-κB-signaling pathway activation [ 26 ], and PM2.5-induced oxidative stress increases ICAM-1 and VCAM-1 expression in human endothelial cells via an ERK/Akt/NF-κB-dependent pathway [ 27 ]. PM2.5 exposure also results in a significant increase in the expression of inflammatory genes and activates p38- and ERK-signaling pathways in the liver of the KKAy mice [ 28 ].…”

Ophiopogonin D attenuates PM2.5‑induced inflammation via suppressing the AMPK/NF‑κB pathway in mouse pulmonary epithelial cells

“…For example, Jeong et al (28) have revealed that the epidermal growth factor receptor/mitogen-activated protein kinase/NF-κB/IL-8 pathway may be a possible mechanism for PM2.5-induced lung toxicity. In addition, Li et al (29) observed that PM2.5 may induce inflammatory responses via the Toll-like receptor 4/p38/NF-κB pathway. Notably, activated NF-κB serves a crucial role in PM2.5-induced inflammatory diseases.…”

Protective effects of VGX-1027 in PM2.5-induced airway inflammation and bronchial hyperresponsiveness

“…In addition, TLR4 can also activate p38 MAPK and thereby drive the post-transcriptional regulation of inflammatory mediators such as TNF-, IL-6 and IL-1 (Singh et al, 2017). Several studies have demonstrated that PM 2.5 activates TLR4-drived p38 MAPK/NF-B signaling pathways and induce the recruitment of inflammatory cells and the release of proinflammatory cytokines (He et al, 2017;Li et al, 2017;Song et al, 2017). Previous studies have also shown that treatment with VGX-1027 inhibits the activation of the TLR4 signaling pathway (Cha et al, 2013;Laird et al, 2014).…”