title: Never deem lightly the "less harmful" low-molecular-weight PAH, NPAH, and OPAH - Disturbance of the immune response at real environmental levels.
abstract: The upcoming energy structure optimization and the implementation of strict emissions control will effectively alleviated the pollution of high-molecular-weight (HMW) polycyclic aromatic hydrocarbons (PAHs) in the atmosphere. Compared to HMW PAHs, the immune response to low-molecular-weight (LMW) PAHs is recognized as "less harmful", despite the high proportions of these substances. The present study intends to investigate the effects of several of the most abundant LMW PAHs on macrophages RAW264.7 at environmentally relevant doses. The data assembled herein showed that Fluoranthene (Fluo, PAH) formed a π-π interaction with the Phe12 residue of AhR while inhibiting the transcription of CYP1A1 and CYP1B1, and ultimately induced the inflammatory cytokines in RAW264.7. The 1-Nitropyrene (1-Nitro, NPAH) formed both a π-π interaction and a hydrogen bond with AhR, stimulated CYP1A1transcription, while suppressed the cytokine levels. Additionally, the inflammation potency caused by TPAHs was highly correlated with the cytotoxic potency rather than the oxidative stress potency. When stimulated by LPS, the transcription of IL-6 was inhibited by Fluo, and 1-Nitro suppressed both IL-6 and TNFα transcription. Furthermore, only 1-Nitro gave a significant inhibition on phagocytosis. The effects of 9-Fluorenone (9-Fluo, OPAH) on macrophages remained insignificant throughout the study since the low affinity for AhR, which resulted in low cytotoxicity. Collectively, this study suggested that LMW PAHs tended to cause mild inflammation when they bind without activating AhR. During infection, AhR ligands caused immunosuppression and this potency for TPAHs may be higher in AhR activator than that in AhR inactivator.
authors.affiliation: College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Cui
authors.initials: C
authors.lastname: Wang
authors.affiliation: College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Jinhuan
authors.initials: J
authors.lastname: Yang
authors.affiliation: Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Linwensi
authors.initials: L
authors.lastname: Zhu
authors.affiliation: College of Environment, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Yan
authors.affiliation: College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.
authors.forename: Dezhao
authors.initials: D
authors.lastname: Lu
authors.affiliation: College of Environment, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: College of Environment, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Meirong
authors.initials: M
authors.lastname: Zhao
authors.affiliation: College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China. Electronic address: lzy@sxu.edu.cn.
authors.forename: Zhuoyu
authors.initials: Z
authors.lastname: Li
mesh_terms: D000393:Air Pollutants / Q000032:analysis / Q000633:toxicity*; D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1 / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005449:Fluorenes / Q000032:analysis / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D051379:Mice; D062105:Molecular Docking Simulation; D008970:Molecular Weight; D018384:Oxidative Stress / Q000187:drug effects / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis / Q000633:toxicity*; D011721:Pyrenes / Q000032:analysis / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D016207:Cytokines; D005449:Fluorenes; D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; D018336:Receptors, Aryl Hydrocarbon; C007738:fluoranthene; C028401:9-fluorenone; C585498:Cyp1b1 protein, mouse; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; C032668:1-nitropyrene
keywords: AhR binding; Environmental relevant level; Low molecular weighted PAHs; Macrophage