Interleukin-4 from curcumin‑activated OECs emerges as a central modulator for increasing M2 polarization of microglia/macrophage in OEC anti‑inflammatory activity for functional repair of spinal cord injury

This study investigates how curcumin-activated olfactory ensheathing cells (aOECs) can help repair spinal cord injuries by reducing inflammation. The research focuses on the role of Interleukin-4 (IL-4) released by aOECs in changing microglia/macrophages from a pro-inflammatory (M1) to an anti-inflammatory (M2) state. The study found that IL-4 is crucial for switching microglia to the M2 phenotype, reducing inflammation and promoting nerve cell survival and growth. Blocking IL-4 reversed these beneficial effects, indicating its central role. The researchers also identified specific signaling pathways (JAK1/STAT1/3/6 and NF-κB/SOCS1/3) that are involved in IL-4's ability to modulate microglial polarization, providing potential targets for new therapies to treat spinal cord injuries by controlling inflammation.

• 1
  Interleukin-4 (IL-4) plays a leading role in triggering the M1 to M2 microglial phenotype, appreciably decreasing the levels of M1 markers and elevating the levels of M2 markers.
• 2
  Blockade of IL-4 signaling by siRNA and a neutralizing antibody in aOEC medium reverses the transition of M1 to M2, and the activated microglia stimulated with the aOEC medium lacking IL-4 significantly decreases neuronal survival and neurite outgrowth.
• 3
  The crosstalk between JAK1/STAT1/3/6-targeted downstream signals and NF-κB/SOCS1/3 signaling predominantly orchestrates IL-4-modulated microglial polarization event.