title: Nanoceria restrains PM2.5-induced metabolic disorder and hypothalamus inflammation by inhibition of astrocytes activation related NF-κB pathway in Nrf2 deficient mice.
abstract: Increasing studies demonstrated that air pollution (PM2.5) plays a significant role in metabolic and neurological diseases. Unfortunately, there is no direct testimony of this, and yet the molecular mechanism by which the occurrence remains unclear. In this regard, we investigated the role of NF-κB and Nrf2 signaling in PM2.5-induced metabolic disorders and neuroinflammation, and further confirmed whether Nrf2 deficiency promoted PM2.5-induced inflammatory response by up regulating astrocytes activation and nerve injury via modulating NF-κB signaling pathways. Present results found that, indeed, PM2.5 challenges results in glucose tolerance, insulin resistance, dysarteriotony, peripheral inflammation, nerve injury and hypothalamus oxidative stress through astrocytes activation related NF-κB pathway in Nrf2 deficient mice. Moreover, in vitro study, we confirmed that activated astrocytes induced by PM2.5 were involved in pathogenesis of hypothalamic inflammation, which were significantly associated with NF-κB signaling. Nanoceria as potential anti-inflammatory and anti-oxidant stress biomaterial has gained increasing attention. Moderate nanoceria treatment is able to restrain PM2.5-induced metabolic syndrome and inflammation. Inhibition of astrocytes activation related NF-κB and enhancement of Nrf2 by cerium oxide were observed in vivo and in vitro, suggesting cerium oxide inhibited hypothalamic inflammation and nerve injury by altering hypothalamic neuroendocrine alterations and decreasing glial cells activation. In addition, NF-κB inhibitor pyrollidine dithiocarbamate (PDTC) treated primary astrocytes directly determined Nrf2 pathway could be up regulated by dose-dependent nanoceria. These results suggest a new therapeutic approach or target to protect against air pollution related diseases by cerium oxide treatment.
authors.affiliation: Fenchem Ingredient Technology Company & Nanjing University, Nanjing 210023, PR China.
authors.forename: Min-Xuan
authors.initials: MX
authors.lastname: Xu
authors.affiliation: Fenchem Ingredient Technology Company & Nanjing University, Nanjing 210023, PR China.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Zhu
authors.affiliation: Fenchem Ingredient Technology Company & Nanjing University, Nanjing 210023, PR China.
authors.forename: Hsiao-Feng
authors.initials: HF
authors.lastname: Chang
authors.affiliation: Research Institute of Leisure Industry, Changzhou University, Changzhou 213164, PR China. Electronic address: bolucy79@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
mesh_terms: D000393:Air Pollutants / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002563:Cerium / Q000494:pharmacology*; D005786:Gene Expression Regulation; D005951:Glucose Tolerance Test; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000172:deficiency / Q000235:genetics*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage; D018384:Oxidative Stress / Q000187:drug effects; D052638:Particulate Matter / Q000037:antagonists & inhibitors* / Q000633:toxicity; D061251:Primary Cell Culture; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D015398:Signal Transduction; D013859:Thiocarbamates / Q000494:pharmacology
chemical_list: D000393:Air Pollutants; D000894:Anti-Inflammatory Agents, Non-Steroidal; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; D052638:Particulate Matter; D013859:Thiocarbamates; C066229:prolinedithiocarbamate; D002563:Cerium; C030583:ceric oxide; D011392:Proline
keywords: NF-κB; Nanoceria; Neuroinflammation; Nrf2; Particulate matter 2.5