title: Activation of microglia by histamine and substance P.
abstract: BACKGROUND
  Activated microglia perform many of the immune effector functions typically associated with macrophages. However, the regulators involved in microglial activation are not well defined. Because microglia play a pivotal role in immune surveillance of the CNS, we studied the effect of the neuromediators histamine and substance P on microglia.
  
  
  METHODS
  The induction of microglial activation by histamine and substance P was examined using primary cultured microglia. Fluorescent images were acquired with a confocal microscope. The levels of TNF-α and IL-6 were measured with a commercial ELISA kit. Intracellular reactive oxygen species (ROS) levels were determined by dichlorodihydrofluorescein oxidation. The mitochondrial membrane potential was assessed with the MitoProbe™ JC-1 assay kit.
  
  
  RESULTS
  We found that the neuromediators histamine and substance P were able to stimulate microglial activation and the subsequent production of ROS and proinflammatory factors TNF-α and IL-6. These effects were partially abolished by antagonists of the histamine receptors H1 and H4 and of the substance P receptors NK-1, NK-2 and NK-3. Histamine induced mitochondrial membrane depolarization in microglia.
  
  
  CONCLUSIONS
  These results indicate that the neuromediators histamine and SP can trigger microglial activation and release of pro-inflammatory factors from microglia, thus contributing to the development of microglia-mediated inflammation in the brain.
authors.affiliation: Clinical Research Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, P. R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
authors.forename: Chen
authors.initials: C
authors.lastname: Qu
authors.forename: Xiang
authors.initials: X
authors.lastname: Lu
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006632:Histamine / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D017628:Microglia / Q000187:drug effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology*; D048069:Tumor Necrosis Factors / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D017382:Reactive Oxygen Species; D048069:Tumor Necrosis Factors; D013373:Substance P; D006632:Histamine