Nargenicin attenuates lipopolysaccharide-induced inflammatory responses in BV-2 cells.
Microglia activation has been considered as a major factor associated with neurodegenerative diseases. In this study, we investigated the inhibitory effects of nargenicin, a natural antibiotic from soil bacterium Nocardia, on lipopolysaccharide (LPS)-induced inflammatory activation of microglia. Nargenicin significantly attenuated LPS-induced nitric oxide production in BV-2 microglial cells. Furthermore, nargenicin effectively suppressed the upregulation of interleukin-1beta, tumor necrosis factor alpha, and inducible nitric oxide synthase at both mRNA and protein levels in LPS-stimulated BV-2 microglia. In addition, nargenicin blocked LPS-induced degradation of IkappaB-alpha, indicating that the initial molecular target of nargenicin is the transcription factor nuclear factor-kappaB. These results suggest that nargenicin should be evaluated as a therapeutic agent for inflammatory neurodegenerative diseases.
Yoo
Jin Cheol
JC
Department of Pharmacy, College of Pharmacy, Chosun University, Gwangju, Korea.
Cho
Hong-Suk
HS
Park
Euteum
E
Park
Jeong Ae
JA
Kim
Seung
S
Kim
Do Kyung
DK
Kim
Chun Sung
CS
Kim
Sung-Jun
SJ
Chun
Hong Sung
HS
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D020672:I-kappa B Proteins / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009615:Nocardia; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D007783:Lactones; D008070:Lipopolysaccharides; C000606205:Nfkbia protein, mouse; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; C034624:nargenicin A1; D052247:Nitric Oxide Synthase Type II