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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Diesel exhaust activates and primes microglia: air pollution, neuroinflammation, and regulation of dopaminergic neurotoxicity.

Authors: Levesque, Shannon; Taetzsch, Thomas; Lull, Melinda E; Kodavanti, Urmila; Stadler, Krisztian; Wagner, Alison; Johnson, Jo Anne; Duke, Laura; Kodavanti, Prasada; Surace, Michael J; Block, Michelle L

Published In Environ Health Perspect, (2011 Aug)

Abstract: Air pollution is linked to central nervous system disease, but the mechanisms responsible are poorly understood.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.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.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 TNFýý (tumor necrosis factor-ýý), IL-1ýý, IL-6, MIP-1ýý (macrophage inflammatory protein-1ýý) 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 TNFýý at 6 hr posttreatment. Although DEP alone failed to cause the production of cytokines and chemokines, DEP (5 ýýg/mL) pretreatment followed by lipopolysaccharide (2.5 ng/mL) in vitro synergistically amplified nitric oxide production, TNFýý release, and DA neurotoxicity. Pretreatment with fractalkine (50 pg/mL) in vitro ameliorated DEP (50 ýýg/mL)-induced microglial hydrogen peroxide production and DA neurotoxicity.Together, these findings reveal complex, interacting mechanisms responsible for how air pollution may cause neuroinflammation and DA neurotoxicity.

PubMed ID: 21561831 Exiting the NIEHS site

MeSH Terms: Air Pollution/adverse effects*; Animals; Calcium-Binding Proteins/metabolism; Chemokine CCL3; Chemokine CX3CL1/pharmacology; Dopaminergic Neurons/drug effects*; Dopaminergic Neurons/metabolism*; Hydrogen Peroxide/metabolism; Inflammation/chemically induced*; Interleukin-1beta/metabolism; Interleukin-6/metabolism; Male; Microfilament Proteins/metabolism; Microglia/drug effects*; Microglia/metabolism*; Rats; Rats, Inbred WKY; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha/metabolism; Vehicle Emissions/toxicity*

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