alexa Activation of microglia by histamine and substance P.
Neurology

Neurology

Journal of Clinical & Experimental Neuroimmunology

Author(s): Zhu J, Qu C, Lu X, Zhang S

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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. © 2014 S. Karger AG, Basel. This article was published in Cell Physiol Biochem and referenced in Journal of Clinical & Experimental Neuroimmunology

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