title: Inhaled ultrafine particulate matter affects CNS inflammatory processes and may act via MAP kinase signaling pathways.
abstract: In addition to evidence that inhalation of ambient particulate matter (PM) can increase cardiopulmonary morbidity and mortality, the brain may also constitute a site adversely effected by the environmental presence of airborne particulate matter. We have examined the association between exposure to PM and adverse CNS effects in apolipoprotein E knockout (ApoE-/-) mice exposed to two levels of concentrated ultrafine particulate matter in central Los Angeles. Mice were euthanized 24h after the last exposure and brain, liver, heart, lung and spleen tissues were collected and frozen for subsequent bioassays. There was clear evidence of aberrant immune activation in the brains of exposed animals as judged by a dose-related increase in nuclear translocation of two key transcription factors, NF-kappaB and AP-1. These factors are involved in the promotion of inflammation. Increased levels of glial fibrillary acidic protein (GFAP) were also found consequent to particulate inhalation suggesting that glial activation was taking place. In order to determine the mechanism by which these events occurred, levels of several MAP kinases involved in activation of these transcription factors were assayed by Western blotting. There were no significant changes in the proportion of active (phosphorylated) forms of ERK-1, IkB and p38. However, the fraction of JNK in the active form was significantly increased in animals receiving the lower concentration of concentrated ambient particles (CAPs). This suggests that the signaling pathway by which these transcription factors are activated involves the activation of JNK.
authors.affiliation: Department of Community and Environmental Medicine, University of California-Irvine, Irvine, CA 92697, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Kleinman
authors.forename: J A
authors.initials: JA
authors.lastname: Araujo
authors.forename: A
authors.initials: A
authors.lastname: Nel
authors.forename: C
authors.initials: C
authors.lastname: Sioutas
authors.forename: A
authors.initials: A
authors.lastname: Campbell
authors.forename: P Q
authors.initials: PQ
authors.lastname: Cong
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: S C
authors.initials: SC
authors.lastname: Bondy
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology*; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007249:Inflammation / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D005904:Glial Fibrillary Acidic Protein; D016328:NF-kappa B; D052638:Particulate Matter; D017392:Thiobarbituric Acid Reactive Substances; D018808:Transcription Factor AP-1; D020928:Mitogen-Activated Protein Kinases