Apelin activates the expression of inflammatory cytokines in microglial BV2 cells via PI-3K/Akt and MEK/Erk pathways

Sci China Life Sci. 2015 Jun;58(6):531-40. doi: 10.1007/s11427-015-4861-0. Epub 2015 May 8.

Abstract

This paper aims to observe the changes of the inflammatory cytokines in microglial BV2 cells stimulated by apelin, and investigate the mechanism of inflammatory cytokines secretion after apelin stimulation. Immunofluorescence and quantitative real-time PCR were performed to observe expression of TNF-α, IL-1β, IL-10, MIP-1α, and MCP-1 in BV2 cells. Western blot was used to investigate the expression of phosphorylation PI-3K/Akt and phosphorylation Erk signaling pathways in BV2 cells after stimulation by apelin. Furthermore, PI-3K/Akt inhibitor (LY294402) and Erk inhibitor (U0126) were used as antagonists to detect the secretion mechanisms of cytokines in BV2 cells stimulated by apelin. Exogenous recombinant apelin activated the expression of TNF-α, IL-1β, MCP-1 and MIP-1α in BV2 cells by the detection of fluorescence expression and mRNA. Apelin also unregulated the protein expression of p-PI-3K/Akt and p-Erk in BV2 cells induced by apelin. LY294002 and U0126 inhibited activation of p-PI-3K/Akt and p-Erk expression by Western blot and attenuated the expression of inflammation factors in BV2 cells by fluorescence staining. This study demonstrates that apelin is a potential activator of inflammation factors through the PI3K/Akt and Erk signaling pathway and is potential therapeutically relevant to inflammatory responses of microglia cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipokines / metabolism*
  • Animals
  • Apelin
  • Apelin Receptors
  • Butadienes / chemistry
  • Chemokine CCL2 / metabolism
  • Chemokine CCL3 / metabolism
  • Chromones / chemistry
  • Enzyme Inhibitors / chemistry
  • Gene Expression Regulation*
  • Inflammation
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Interleukin-10 / metabolism
  • Interleukin-1beta / metabolism
  • Mice
  • Microglia / metabolism
  • Microscopy, Fluorescence
  • Morpholines / chemistry
  • Nitriles / chemistry
  • Phosphatidylinositol 3-Kinases / metabolism
  • Real-Time Polymerase Chain Reaction
  • Receptors, G-Protein-Coupled / metabolism*
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Adipokines
  • Apelin
  • Apelin Receptors
  • Apln protein, mouse
  • Aplnr protein, mouse
  • Butadienes
  • Ccl2 protein, mouse
  • Ccl3 protein, mouse
  • Chemokine CCL2
  • Chemokine CCL3
  • Chromones
  • Enzyme Inhibitors
  • IL10 protein, mouse
  • IL1B protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • Interleukin-1beta
  • Morpholines
  • Nitriles
  • Receptors, G-Protein-Coupled
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • U 0126
  • Interleukin-10
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Phosphatidylinositol 3-Kinases