DJ-1 mutation decreases astroglial release of inflammatory mediators

Authors

• A K. Ashley, The Center for Environmental Medicine, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1680, United States.
• A I. Hinds, The Center for Environmental Medicine, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1680, United States.
• W H. Hanneman, The Center for Environmental Medicine, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1680, United States.
• R B. Tjalkens, The Center for Environmental Medicine, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523-1680, United States.
• M E. Legare, 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.

Document Type

Article

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.

Keywords

Astrocyte, DJ-1, Lipopolysaccharide, Neuroinflammation

Medical Subject Headings

Animals; Anthracenes (pharmacology); Astrocytes (drug effects, metabolism); Butadienes (pharmacology); Cyclooxygenase 2 (biosynthesis); Dinoprostone (metabolism); Imidazoles (pharmacology); Inflammation Mediators (metabolism); Lipopolysaccharides; Mice; Mice, Knockout; Nitric Oxide (metabolism); Nitric Oxide Synthase Type II (biosynthesis); Nitriles (pharmacology); Primary Cell Culture; Protein Deglycase DJ-1 (genetics); Pyridines (pharmacology); Tumor Necrosis Factor-alpha (biosynthesis, metabolism)

Publication Date

1-1-2016

Publication Title

Neurotoxicology

E-ISSN

1872-9711

Volume

52

First Page

198

Last Page

203

PubMed ID

26691871

Digital Object Identifier (DOI)

10.1016/j.neuro.2015.12.007

Recommended Citation

Ashley, A K.; Hinds, A I.; Hanneman, W H.; Tjalkens, R B.; and Legare, M E., "DJ-1 mutation decreases astroglial release of inflammatory mediators" (2016). Translational Neuroscience. 2518.
https://scholar.barrowneuro.org/neurobiology/2518