Mechanisms of anti-inflammatory property of conserved dopamine neurotrophic factor: inhibition of JNK signaling in lipopolysaccharide-induced microglia.
Microglia are important resident immune cells in the central nervous system (CNS) and involved in the neuroinflammation caused by CNS disorders, including brain trauma, ischemia, stroke, infections, inflammation, and neurodegenerative diseases. Our study explores the hypothesis that conserved dopamine neurotrophic factor (CDNF), a secretory neurotrophic factor, may provide a novel therapy for associated with neuroinflammation related to the microglia. We observed that CDNF was upregulated in rat primary microglia treated with 1 μg/mL lipopolysaccharide, an inflammatory inducer, for 24 h. Thus, we hypothesize that CDNF may play a role, mediator or inhibitor, in regulating the inflammation in microglial cells induced by LPS. Finally, our data showed that CDNF significantly attenuated the production of proinflammatory cytokines (PGE2 and IL-1β) and remarkably alleviated the cytotoxicity (percentage of lactate dehydrogenase released) in the LPS-induced microglia by suppressing the phosphorylation of JNK, but not the P38 or ERK pathways. These results demonstrate the anti-inflammatory property of CDNF by inhibition of JNK signaling in LPS-induced microglia, suggesting that CDNF may be a potential novel agent for the treatment of neuroinflammation in the CNS disorders.
Hua
H
Zhao
Lei
L
Cheng
Yi
Y
Liu
Wen
W
Zhang
Sailendra
S
Maharjan
Zhaoqiang
Z
Cui
Xingli
X
Wang
Dongqi
D
Tang
Lin
L
Nie
D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
C577430:CDNF protein, rat; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D009414:Nerve Growth Factors; D048670:MAP Kinase Kinase 4; D015232:Dinoprostone