| First Author | Ashley AK | Year | 2016 |
| Journal | Neurotoxicology | Volume | 52 |
| Pages | 198-203 | PubMed ID | 26691871 |
| Mgi Jnum | J:330091 | Mgi Id | MGI:6840679 |
| Doi | 10.1016/j.neuro.2015.12.007 | Citation | Ashley AK, et al. (2016) DJ-1 mutation decreases astroglial release of inflammatory mediators. Neurotoxicology 52:198-203 |
| abstractText | 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 1mug/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 alpha (TNFalpha). 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 TNFalpha; however, DJ-1(-/-) astrocytes had consistently lower expression compared to DJ-1(+/+) counterparts. Secretion of TNFalpha 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. |
