Diesel Exhaust Activates and Primes Microglia: Air Pollution, Neuroinflammation, and Regulation of Dopaminergic Neurotoxicity

Autor: Michael J. Surace, Shannon Levesque, Michelle L. Block, Krisztian Stadler, Thomas Taetzsch, Jo Anne Johnson, Urmila P. Kodavanti, Melinda E. Lull, Prasada Rao S. Kodavanti, Alison F. Wagner, Laura Duke
Rok vydání: 2011
Předmět:
Male
Chemokine
Health
Toxicology and Mutagenesis
air pollution
Interleukin-1beta
microglia
010501 environmental sciences
Pharmacology
medicine.disease_cause
Rats
Inbred WKY
01 natural sciences
neuroinflammation
Rats
Sprague-Dawley
chemistry.chemical_compound
0302 clinical medicine
oxidative stress
Chemokine CCL3
Vehicle Emissions
biology
Microglia
Microfilament Proteins
3. Good health
medicine.anatomical_structure
Tumor necrosis factor alpha
medicine.symptom
brain
Inflammation
Nitric oxide
03 medical and health sciences
medicine
Animals
Neuroinflammation
0105 earth and related environmental sciences
Chemokine CX3CL1
Interleukin-6
Tumor Necrosis Factor-alpha
Research
Dopaminergic Neurons
Calcium-Binding Proteins
Public Health
Environmental and Occupational Health
Neurotoxicity
Hydrogen Peroxide
medicine.disease
Rats
chemistry
13. Climate action
Immunology
Parkinson’s disease
biology.protein
030217 neurology & neurosurgery
Oxidative stress
Zdroj: Environmental Health Perspectives
ISSN: 1552-9924
0091-6765
Popis: Background: Air pollution is linked to central nervous system disease, but the mechanisms responsible are poorly understood. Objectives: Here, we sought to address the brain-region–specific effects of diesel exhaust (DE) and key cellular mechanisms underlying DE-induced microglia activation, neuroinflammation, and dopaminergic (DA) neurotoxicity. Methods: Rats were exposed to DE (2.0, 0.5, and 0 mg/m3) by inhalation over 4 weeks or as a single intratracheal administration of DE particles (DEP; 20 mg/kg). Primary neuron–glia cultures and the HAPI (highly aggressively proliferating immortalized) microglial cell line were used to explore cellular mechanisms. Results: Rats exposed to DE by inhalation demonstrated elevated levels of whole-brain IL-6 (interleukin-6) protein, nitrated proteins, and IBA-1 (ionized calcium-binding adaptor molecule 1) protein (microglial marker), indicating generalized neuroinflammation. Analysis by brain region revealed that DE increased TNFα (tumor necrosis factor-α), IL-1β, IL-6, MIP-1α (macrophage inflammatory protein-1α) RAGE (receptor for advanced glycation end products), fractalkine, and the IBA-1 microglial marker in most regions tested, with the midbrain showing the greatest DE response. Intratracheal administration of DEP increased microglial IBA-1 staining in the substantia nigra and elevated both serum and whole-brain TNFα at 6 hr posttreatment. Although DEP alone failed to cause the production of cytokines and chemokines, DEP (5 μg/mL) pretreatment followed by lipopolysaccharide (2.5 ng/mL) in vitro synergistically amplified nitric oxide production, TNFα release, and DA neurotoxicity. Pretreatment with fractalkine (50 pg/mL) in vitro ameliorated DEP (50 μg/mL)-induced microglial hydrogen peroxide production and DA neurotoxicity. Conclusions: Together, these findings reveal complex, interacting mechanisms responsible for how air pollution may cause neuroinflammation and DA neurotoxicity.
Databáze: OpenAIRE
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