Interleukin-1beta and interleukin-6 stimulate matrix metalloproteinase-9 secretion in cultured myenteric glia

Theodore Lin1, Weizhen Zhang, Yongyi Fan

  • 1Department of Surgery, University of Michigan Medical Center, Ann Arbor, Michigan, USA.

Insights

Myenteric glia secrete matrix metalloproteinases (MMPs) when stimulated by cytokines like interleukin-1beta (IL-1beta) and interleukin-6 (IL-6). These findings highlight glia

Area of Science:

  • Neuroimmunology
  • Gastroenterology
  • Cell Biology

Background:

  • Myenteric glia, crucial for gut homeostasis, express glial fibrillary acidic protein (GFAP).
  • Cytokines like IL-1beta and IL-6 play roles in neuroinflammation and gastrointestinal function.
  • Matrix metalloproteinases (MMPs) are enzymes involved in extracellular matrix remodeling and signaling.

Purpose of the Study:

  • To investigate the effect of IL-1beta and IL-6 on MMP secretion by cultured myenteric glia.
  • To determine the biological activity and localization of secreted MMPs.

Main Methods:

  • Primary cultures of myenteric glia were established and characterized.
  • Cells were stimulated with IL-1beta and IL-6.
  • Western blotting and gelatin zymography were used to analyze MMP-9 and MMP-2 secretion.
  • Immunocytochemistry was performed to detect intracellular MMP-9 localization.

Main Results:

  • IL-1beta and IL-6 stimulation significantly increased MMP-9 secretion by myenteric glia compared to controls.
  • MMP-2 was constitutively secreted by both control and cytokine-stimulated glia.
  • Gelatin zymography confirmed the biological activity of the secreted MMPs.
  • Intracellular MMP-9 staining was observed in cytokine-stimulated cells, but not in controls.

Conclusions:

  • Cultured myenteric glia are responsive to IL-1beta and IL-6.
  • These glia secrete biologically active MMPs, particularly MMP-9, upon cytokine stimulation.
  • These findings suggest a role for myenteric glia in modulating the extracellular environment through MMP secretion in response to inflammatory signals.