Effects of Nogo-A Silencing on TNF-α and IL-6 Secretion and TH Downregulation in Lipopolysaccharide-Stimulated PC12 Cells.

Abstract	Parkinson's disease (PD) is a common degenerative disease that lacks efficient treatment. Myelin-associated neurite outgrowth inhibitor A (Nogo-A) is relevant with inhibition of nerve regeneration and may play vital role in pathogenesis of PD. The study aimed to establish the shRNA expression plasmids of Nogo-A gene and explore the regulatory effects of Nogo-A silencing on the expression of inflammation factor tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) as well as tyrosine hydroxylase (TH) in lipopolysaccharide- (LPS-) stimulated rat PC12 cells. The results showed that both mRNA and protein levels of Nogo-A in pGenesil-nogoA-shRNA group were downregulated. The viabilities of PC12 cells decreased with increase of LPS concentrations. LPS significantly increased the supernatant TNF-alpha and IL-6 concentrations and reduced TH protein expression in PC12 cells, while silencing Nogo-A could block these effects. These results suggested that LPS can activate PC12 cells to secrete inflammatory cytokines and lower the TH expression, which can be regulated by Nogo-A gene silencing. Nogo-A silencing might provide new ideas for PD treatment in the future.
Authors	Jianbin Zhong, Shengnuo Fan, Zhenwen Yan, Songhua Xiao, Limei Wan, Chibang Chen, Simin Zhong, Lu Liu, Jun Liu
Journal	BioMed research international (Biomed Res Int) Vol. 2015 Pg. 817914 ( 2015) ISSN: 2314-6141 [Electronic] United States
PMID	26583134 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Interleukin-6 Lipopolysaccharides Myelin Proteins Nogo Proteins RNA, Messenger RTN4 protein, human Rtn4 protein, rat Tumor Necrosis Factor-alpha Tyrosine 3-Monooxygenase
Topics	Animals Gene Expression Regulation (drug effects) Gene Silencing Humans Inflammation (chemically induced, genetics, pathology) Interleukin-6 (genetics, metabolism) Lipopolysaccharides (toxicity) Myelin Proteins (antagonists & inhibitors, genetics) Nerve Regeneration (genetics) Nogo Proteins PC12 Cells Parkinson Disease (genetics, pathology, therapy) RNA, Messenger (biosynthesis) Rats Tumor Necrosis Factor-alpha (genetics, metabolism) Tyrosine 3-Monooxygenase (biosynthesis, genetics)

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