Neuromelanin inhibits CXCL10 expression in human astroglial cells.
Increasing evidence indicates neuroinflammation is instrumental in the pathogenesis of Parkinson's disease (PD). In PD, there is selective degeneration of neuromelanin (NM)-containing dopamine neurons. Neuromelanin is predominantly cytoprotective within dopaminergic neurons, whereas, NM released from damaged neurons activates microglia. However, the effects of NM on astroglial cells remain largely unknown. Astroglia are essential to neuronal homeostasis and responsive to injury, in part, through secretion of chemokines, including interferon γ inducible protein-10 (CXCL10). Thus, we used an in vitro approach to identify the effects of NM on TNFα-induced CXCL10 expression in human astroglial cells. TNFα-induced CXCL10 expression was inhibited in NM exposed cells. Additionally, TNFα-induced NF-кB activation was inhibited by NM. Given that CXCL10 expression is NF-кB-dependent in human astroglial cells, these findings suggest that NM may inhibit CXCL10 expression, in part, through an NF-кB-dependent mechanism. While the in vivo consequences of NM mediated effects on astroglial CXCL10 expression remain to be fully elucidated, insights obtained in this study further our understanding of the effects of NM on inflammatory signaling in human astroglial cells.
Tousi
Neda Saffarian
NS
Department of Pharmacology/Physiology, Oklahoma State University Center for Health Sciences, Tulsa, OK 74107, United States.
Buck
Daniel J
DJ
Zecca
Luigi
L
Davis
Randall L
RL
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D002460:Cell Line; D054357:Chemokine CXCL10 / Q000096:biosynthesis*; D006801:Humans; D008543:Melanins / Q000494:pharmacology*; D016328:NF-kappa B / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D008543:Melanins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C014121:neuromelanin