title: Lidocaine attenuates lipopolysaccharide-induced inflammatory responses in microglia.
abstract: BACKGROUND
  Lidocaine has been used as a local anesthetic with anti-inflammatory properties, but its effects on neuroinflammation have not been well defined. In the present study, we investigated the prophylactic effects of lidocaine on lipopolysaccharide (LPS)-activated microglia and explored the underlying mechanisms.
  
  
  METHODS
  Microglial cells were incubated with or without 1 μg/mL LPS in the presence or absence of lidocaine, a p38 mitogen-activated protein kinase (p38 MAPK) inhibitor (SB203580), a nuclear factor-kappa B (NF-κB) inhibitor (pyrrolidine dithiocarbamate), or small interfering RNA. The protein and expression levels of inflammatory mediators, such as monocyte chemotactic protein 1, nitric oxide, prostaglandin E2, interleukin 1β, and tumor necrosis factor α were measured using enzyme-linked immunosorbent assays and real-time polymerase chain reaction. The effect of lidocaine on NF-κB and p38 MAPK activation was evaluated using enzyme-linked immunosorbent assays, Western blot analysis, and electrophoretic mobility shift assay.
  
  
  RESULTS
  Lidocaine (≥2 μg/mL) significantly inhibited the release and expression of nitric oxide, monocyte chemotactic protein 1, prostaglandin E2, interleukin 1β, and tumor necrosis factor α in LPS-activated microglia. Treatment with lidocaine also significantly inhibited the phosphorylation of p38 MAPK and the nuclear translocation of NF-κB p50/p65, increased the protein levels of inhibitor kappa B-α. Furthermore, our study shows that the LPS-induced release of inflammatory mediators was suppressed by SB203580, pyrrolidine dithiocarbamate, and small interfering RNA.
  
  
  CONCLUSIONS
  Prophylactic treatment with lidocaine inhibits LPS-induced release of inflammatory mediators from microglia, and these effects may be mediated by blockade of p38 MAPK and NF-κB signaling pathways.
authors: Department of Anesthesiology, First Hospital of Jilin University, Changchun, Jilin, China.
authors: Tong
authors: T
authors: Yuan
authors: Department of Anesthesiology, First Hospital of Jilin University, Changchun, Jilin, China.
authors: Zhiwen
authors: Z
authors: Li
authors: Department of Anesthesiology, First Hospital of Jilin University, Changchun, Jilin, China.
authors: Xinbai
authors: X
authors: Li
authors: Department of Anesthesiology, First Hospital of Jilin University, Changchun, Jilin, China.
authors: Gaoqi
authors: G
authors: Yu
authors: Department of Anesthesiology, First Hospital of Jilin University, Changchun, Jilin, China.
authors: Na
authors: N
authors: Wang
authors: Department of Anesthesiology, First Hospital of Jilin University, Changchun, Jilin, China. Electronic address: qulianguo@outlook.com.
authors: Xige
authors: X
authors: Yang
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D008012:Lidocaine / Q000494:pharmacology* / Q000633:toxicity; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide / Q000378:metabolism; D061251:Primary Cell Culture; D011725:Pyridines / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D013859:Thiocarbamates / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
chemical_list: D000779:Anesthetics, Local; D000975:Antioxidants; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D020672:I-kappa B Proteins; D007093:Imidazoles; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C000606206:Nfkbia protein, rat; D011725:Pyridines; D011759:Pyrrolidines; D034741:RNA, Small Interfering; D013859:Thiocarbamates; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; C020972:pyrrolidine dithiocarbamic acid; D009569:Nitric Oxide; D008012:Lidocaine; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580
keywords: Inflammation; Lidocaine; Lipopolysaccharides; Microglia; NF-kappa B; p38 MAPK