Tumor necrosis factor-α-stimulated brain pericytes possess a unique cytokine and chemokine release profile and enhance microglial activation

Neurosci Lett. 2014 Aug 22:578:133-8. doi: 10.1016/j.neulet.2014.06.052. Epub 2014 Jun 30.

Abstract

Brain pericytes are involved in neurovascular dysfunction, neurodegeneration and/or neuroinflammation. In the present study, we focused on the proinflammatory properties of brain pericytes to understand their participation in the induction of inflammation at the neurovascular unit (NVU). The NVU comprises different cell types, namely, brain microvascular endothelial cells, pericytes, astrocytes and microglia. Among these, we found pericytes to be the most sensitive to tumor necrosis factor (TNF)-α, possessing a unique cytokine and chemokine release profile. This was characterized by marked release of interleukin (IL)-6 and macrophage inflammatory protein-1α. Furthermore, TNF-α-stimulated pericytes induced expression of inducible nitric oxide synthase and IL-1β mRNAs, as an index of BV-2 microglial cell activation state, to the highest levels. Based on these findings, the possibility that brain pericytes act specifically as TNF-α-sensitive cells and as effectors of TNF-α through the release of proinflammatory factors, and that, as such, they have a role in inducing brain inflammation, should be considered.

Keywords: Blood–brain barrier; Brain inflammation; Microglia; Neurovascular unit; Pericytes; Tumor necrosis factor-α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Blood-Brain Barrier / metabolism*
  • Chemokines / metabolism*
  • Cytokines / metabolism*
  • Encephalitis / metabolism*
  • Endothelial Cells / metabolism
  • Interleukin-1beta / metabolism
  • Microglia / metabolism*
  • Nitric Oxide Synthase / metabolism
  • Pericytes / drug effects
  • Pericytes / metabolism*
  • Primary Cell Culture
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Chemokines
  • Cytokines
  • Interleukin-1beta
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide Synthase