Anti-inflammatory effects of catechols in lipopolysaccharide-stimulated microglia cells: inhibition of microglial neurotoxicity.
Microglial activation plays a pivotal role in the pathogenesis of neurodegenerative diseases by producing various proinflammatory cytokines and nitric oxide (NO). In the present study, the anti-inflammatory and subsequent neuroprotective effects of catechol and its derivatives including 3-methylcatechol, 4-methylcatechol, and 4-tert-butylcatechol were investigated in microglia and neuroblastoma cells in culture. The four catechol compounds showed anti-inflammatory effects with different potency. The catechols significantly decreased lipopolysaccharide (LPS)-induced NO and tumor necrosis factor (TNF)-alpha production in BV-2 microglia cells. The catechols also inhibited the expression of inducible nitric oxide synthase (iNOS) and TNF-alpha at mRNA or protein levels in the LPS-stimulated BV-2 cells. In addition, the catechols inhibited LPS-induced nuclear translocation of p65 subunit of nuclear factor (NF)-kappaB, IkappaB degradation, and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in BV-2 cells. Moreover, the catechols attenuated the cytotoxicity of LPS-stimulated BV-2 microglia toward co-cultured rat B35 neuroblastoma cells. The catechols, however, did not protect B35 cells against H(2)O(2) toxicity, indicating that the compounds exerted the neuroprotective effect by inhibiting the inflammatory activation of microglia in the co-culture. The anti-inflammatory and neuroprotective properties of the catechols in cultured microglia and neuroblastoma cells suggest a therapeutic potential of these compounds for the treatment of neurodegenerative diseases that are associated with an excessive microglial activation.
Zheng
Long Tai
LT
Department of Pharmacology, Brain Science and Engineering Institute, CMRI, Kyungpook National University School of Medicine, 101 Dong-In, Joong-gu, Daegu, 700-422, Republic of Korea.
Ryu
Geun-Mu
GM
Kwon
Byoung-Mog
BM
Lee
Won-Ha
WH
Suk
Kyoungho
K
D000893:Anti-Inflammatory Agents; D015153:Blotting, Western; D002396:Catechols / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006801:Humans; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D017628:Microglia / Q000187:drug effects*; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D020258:Neurotoxicity Syndromes / Q000517:prevention & control*; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009573:Nitrites / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D000893:Anti-Inflammatory Agents; D002396:Catechols; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009573:Nitrites; D013778:Tetrazolium Salts; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases; C022616:thiazolyl blue