Allograft inflammatory factor-1 released from the cerebral microglia affect several organs in the body

Mai Fukasawa1,2, Kensuke Nishio1,2, Daichi Oikawa1,2

  • 1Department of Complete Denture Prosthodontics, Nihon University School of Dentistry, Tokyo, Japan.

Insights

Allograft inflammatory factor-1 (AIF-1) is upregulated in microglia following cerebral ischemia. This increased AIF-1 production in microglia may regulate its own expression through an autocrine mechanism.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Allograft inflammatory factor-1 (AIF-1) is a calcium-binding protein expressed in myeloid cells, particularly microglia.
  • Microglia play critical roles in brain inflammation and injury, including in conditions like cerebral ischemia.
  • Understanding the regulation of AIF-1 in microglia is crucial for developing therapeutic strategies for neurological disorders.

Purpose of the Study:

  • To investigate the mechanisms regulating Allograft inflammatory factor-1 (AIF-1) expression in microglia during cerebral ischemia.
  • To determine the role of AIF-1 in microglia activation and its potential autocrine signaling in the context of ischemia.

Main Methods:

  • Unilateral common carotid artery occlusion (UCCAO) model in C57BL/6 male mice.
  • Immunohistochemistry to detect AIF-1 and Iba-1 (microglia marker) expression.
  • Enzyme-linked immunosorbent assay (ELISA) for quantifying AIF-1 levels in brain homogenates and serum.
  • Real-time PCR to analyze AIF-1 mRNA expression.
  • In vitro studies using murine microglia cell line (MG6) under hypoxic conditions and stimulation with recombinant AIF-1.
  • Minocycline treatment to assess microglia activation-dependent effects.

Main Results:

  • UCCAO significantly increased AIF-1 expression in microglia within the brain.
  • AIF-1 production was regulated at the transcriptional level, with elevated serum levels observed early after UCCAO.
  • Increased Iba-1 immunoreactivity indicated widespread microglia activation in various organs, notably the spleen.
  • Minocycline treatment reduced Iba-1 positive cell accumulation, confirming microglia activation dependence.
  • In vitro, hypoxia upregulated AIF-1 mRNA and secretion in MG6 cells.
  • Recombinant AIF-1 stimulation induced AIF-1 mRNA expression in MG6 cells, suggesting autocrine regulation.

Conclusions:

  • Cerebral ischemia induces significant upregulation of AIF-1 in microglia at both protein and mRNA levels.
  • AIF-1 plays a role in microglia activation and accumulation in response to ischemic injury.
  • Microglia-derived AIF-1 may regulate its own expression through an autocrine feedback loop, particularly under hypoxic conditions.