title: Papaverine inhibits lipopolysaccharide-induced microglial activation by suppressing NF-κB signaling pathway.
abstract: OBJECTIVE
  To investigate the effects of papaverine (PAP) on lipopolysaccharide (LPS)-induced microglial activation and its possible mechanisms.
  
  
  METHODS
  BV2 microglial cells were first pretreated with PAP (0, 0.4, 2, 10, and 50 μg/mL) and then received LPS stimulation. Transcription and production of proinflammatory factors (IL1β, TNFα, iNOS, and COX-2) were used to evaluate microglial activation. The transcriptional changes undergone by M1/M2a/M2b markers were used to evaluate phenotype transformation of BV2 cells. Immunofluorescent staining and Western blot were used to detect the location and expression of P65 and p-IKK in the presence or absence of PAP pretreatment.
  
  
  RESULTS
  Pretreatment with PAP significantly inhibited the expression of IL1β and TNFα, and suppressed the transcription of M1/M2b markers Il1rn, Socs3, Nos2 and Ptgs2, but upregulated the transcription of M2a markers (Arg1 and Mrc1) in a dose-dependent manner. In addition, PAP pretreatment significantly decreased the expression of p-IKK and inhibited the nuclear translocation of P65 after LPS stimulation.
  
  
  CONCLUSIONS
  PAP not only suppressed the LPS-induced microglial activity by inhibiting transcription/production of proinflammatory factors, but also promoted the transformation of activated BV2 cells from cytotoxic phenotypes (M1/M2b) to a neuroprotective phenotype (M2a). These effects were probably mediated by NF-κB signaling pathway. Thus, it would be a promising candidate for the treatment of neurodegenerative diseases.
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
authors.forename: Yalong
authors.initials: Y
authors.lastname: Dang
authors.affiliation: Department of Ophthalmology, Yellow-River Hospital, Sanmenxia City, People's Republic of China.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Mu
authors.affiliation: Clinical Laboratory, Yellow-River Hospital, Sanmenxia City, People's Republic of China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology, Yellow-River Hospital, Sanmenxia City, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Ophthalmology, Yellow-River Hospital, Sanmenxia City, People's Republic of China; Clinical Laboratory, Yellow-River Hospital, Sanmenxia City, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Luo
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010207:Papaver / Q000737:chemistry; D010208:Papaverine / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D010208:Papaverine
keywords: microglia; neuroinflammation; neuroprotection; papaverine