Macrophage migration inhibitory factor facilitates prostaglandin E2 production of astrocytes to tune inflammatory milieu following spinal cord injury

Following spinal cord injury, astrocytes, a type of brain cell, produce substances that can either promote or reduce inflammation to maintain a stable environment. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory substance that increases in the injured spinal cord. This study found that MIF helps astrocytes produce prostaglandin E2 (PGE2), which then regulates the inflammatory environment after spinal cord injury. This suggests that MIF's effects on astrocytes could be a target for treating inflammation in the central nervous system. The study showed that MIF activates a specific pathway in astrocytes involving COX2 and PGE2, which in turn affects the production of inflammatory substances by immune cells called macrophages. This process helps to fine-tune the inflammatory response and maintain balance in the injured spinal cord.

• 1
  MIF and COX2 protein levels increased synchronously after spinal cord injury in rats. Blocking MIF reduced COX2 and mPGES-1 expression, leading to decreased PGE2 production.
• 2
  Astrocytes respond to MIF by activating the MAPK/COX2/PGE2 signaling pathway via the CD74 receptor. Inhibiting CD74 reduces COX2 and mPGES-1 protein levels, consequently inhibiting PGE2 production.
• 3
  PGE2 produced by astrocytes suppresses TNF-α production while boosting IL-1β and IL-6 production in LPS-activated macrophages. This suggests PGE2 fine-tunes the inflammatory response.