Proinflammatory Responses of 1-Nitropyrene against RAW264.7 Macrophages through Akt Phosphorylation and NF-κB Pathways

Ping-Kun Tsai,Rosa Huang-Liu,Chun-Jung Chen,Yu-Hsiang Kuan,Shih-Pin Chen,Wen-Ying Chen,Yan-Yan Ng

doi:10.3390/toxics9110276

Abstract

Air pollution is a major environmental and public health problem worldwide. A nitro-polycyclic aromatic hydrocarbon and the most abundant air pollutant in diesel engine exhaust, 1-nitropyrene (1-NP), is caused by the incomplete combustion of carbonaceous organic substances. Macrophages are effector cells of the innate immune cells that provide resistance in the peripheral tissue. The overactivation of macrophages results in inflammation. The generation of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumour necrosis factor alpha, is induced by 1-NP in a concentration-dependent manner in macrophages. In this study, the production of proinflammatory mediators, such as nitrogen oxide and prostaglandin E2, was induced by 1-NP in a concentration-dependent manner through the expression of iNOS and COX2. The generation of proinflammatory cytokines, iNOS, and COX2 was induced by 1-NP through nuclear factor (NF)-κB p65 phosphorylation and the degradation of its upstream factor, IκB. Finally, Akt phosphorylation was induced by 1-NP in a concentration-dependent manner. These findings suggest that 1-NP exhibits a proinflammatory response through the NF-κB pathway activation due to Akt phosphorylation.

Highlights

Air pollution is caused by a mixture of pollutants floating in the atmosphere
Proinflammatory cytokine inhibition presented in a concentrationdependent manner and a significant increase was seen starting at 10 μM (p < 0.05)
After RAW264.7 macrophages had been incubated with 1-NP for 12 h, prostaglandin E2 (PGE2) and nitrogen oxide (NO) were generated in a concentration-dependent manner and a significant increase was observed at 10 μM (p < 0.05, Figure 2). inducible nitric oxide synthase (iNOS) is the upstream factor of NO generation

Summary

Introduction

Air pollution is caused by a mixture of pollutants floating in the atmosphere. These pollutants are generated from natural events, such as fires, storms, volcanic eruptions, and the release of pollen. A major source of air pollutants is human activity, such as fossil fuel combustion, agricultural activity, manufacturing ( in the form of factory exhausts), and mining [1,2,3]. Genotoxicity and apoptosis are induced by 1-NP in macrophages, liver and lung epithelial cells, and hepatoma cells [8,9,10,11,12]. Cytokines and chemokines are induced by 1-NP in the alveolar epithelial cell line A549 and the human bronchial epithelial cell line BEAS-2B [14,15]

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