title: DJ-1 mutation decreases astroglial release of inflammatory mediators.
abstract: Mutations in DJ-1, reactive gliosis and concomitant inflammatory processes are implicated in the pathogenesis and progression of Parkinson's disease (PD). To study the physiological consequences of DJ-1 mutation in the context of neuroinflammatory insult, primary cortical astrocytes were isolated from DJ-1 knockout mice. Astrocytes were exposed to 1μg/mL lipopolysaccharide (LPS) for 24h following 2h pre-exposure to inhibitors of MEK (U0126), JNK (JNK inhibitor II) or p38 (SB203580). Real-time PCR was used to assess the LPS-induced expression of pro-inflammatory mediators cyclooxygenase 2 (COX2), inducible nitric oxide synthetase (NOS2), and tumor necrosis factor α (TNFα). LPS-induced expression of COX2 decreased similarly in DJ-1(+/+) and DJ-1(-/-) astrocytes in response to inhibition of p38, but was unaffected by inhibition of MEK or JNK. No significant alterations in NOS2 expression were observed in any inhibitor-treated cells. The inhibitors did not affect expression of TNFα; however, DJ-1(-/-) astrocytes had consistently lower expression compared to DJ-1(+/+) counterparts. Secretion of TNFα and prostaglandin E2 (PGE2) into the culture medium was significantly decreased in DJ-1(-/-) astrocytes, and inhibition of p38 decreased this secretion in both genotypes. In conclusion, DJ-1(-/-) astrocytes may provide decreased neuroprotection to surrounding neurons due to alterations in pro-inflammatory mediator expression.
authors.affiliation: The Center for Environmental Medicine, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1680, United States.
authors.forename: A K
authors.initials: AK
authors.lastname: Ashley
authors.affiliation: The Center for Environmental Medicine, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1680, United States.
authors.forename: A I
authors.initials: AI
authors.lastname: Hinds
authors.affiliation: The Center for Environmental Medicine, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1680, United States.
authors.forename: W H
authors.initials: WH
authors.lastname: Hanneman
authors.affiliation: The Center for Environmental Medicine, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1680, United States.
authors.forename: R B
authors.initials: RB
authors.lastname: Tjalkens
authors.affiliation: The Center for Environmental Medicine, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1680, United States. Electronic address: marie.legare@colostate.edu.
authors.forename: M E
authors.initials: ME
authors.lastname: Legare
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002070:Butadienes / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D015232:Dinoprostone / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D009570:Nitriles / Q000494:pharmacology; D061251:Primary Cell Culture; D000071617:Protein Deglycase DJ-1 / Q000235:genetics*; D011725:Pyridines / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D000873:Anthracenes; D002070:Butadienes; D007093:Imidazoles; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009570:Nitriles; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; C113580:U 0126; C432165:pyrazolanthrone; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1; D015232:Dinoprostone; C093642:SB 203580
keywords: Astrocyte; DJ-1; Lipopolysaccharide; Neuroinflammation