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Updated: Aug 13, 2026

Analyzing Murine Schwann Cell Development Along Growing Axons
Published on: November 21, 2012
Interleukin-6 production by Schwann cells and induction in sciatic nerve injury
L M Bolin1, A N Verity, J E Silver
1DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304-1104.
Insights
Schwann cells, a type of nerve cell, produce Interleukin-6 (IL-6) when stimulated. This IL-6 promotes neuronal differentiation and aids in nerve regeneration after injury.
Area of Science:
- Neuroscience
- Cell Biology
- Immunology
Background:
- Schwann cells are crucial for peripheral nerve function and regeneration.
- Interleukin-6 (IL-6) is a cytokine with diverse roles in inflammation and cell differentiation.
- The role of IL-6 in Schwann cell biology and nerve regeneration is not fully understood.
Purpose of the Study:
- To investigate the production and function of IL-6 by Schwann cells.
- To determine the stimuli that induce IL-6 production in Schwann cells.
- To explore the role of IL-6 in peripheral nerve regeneration in vivo.
Main Methods:
- Coculture of immortalized Schwann cells (iSC) with PC12 cells.
- Northern blot analysis to detect IL-6 mRNA expression.
- Neutralization assays using anti-IL-6 antisera.
- In vivo sciatic nerve crush injury model.
Main Results:
- iSC produced IL-6 when cocultured with PC12 cells, inducing neuronal differentiation.
- IL-6 production was induced by various stimuli, including lipopolysaccharide and tumor necrosis factor-alpha.
- IL-6 mRNA was upregulated in the sciatic nerve distal to a crush injury within 12 hours.
Conclusions:
- Schwann cells produce IL-6 in response to cellular interactions and inflammatory stimuli.
- IL-6 produced by Schwann cells can promote neuronal differentiation.
- IL-6 induction in Schwann cells following nerve injury suggests a role in peripheral nerve regeneration.
Abstract:
Interleukin-6 (IL-6) was produced by the spontaneously immortal Schwann cell clone, iSC, when cocultured with PC12 cells. The iSC cell-derived IL-6 in coculture conditioned media caused the neuronal differentiation of naive PC12 cells and this bioactivity was neutralized by preincubation of conditioned media with antisera to IL-6. Cocultured iSC transcribe IL-6 message as confirmed by northern analysis. Stimuli that induce IL-6 production in the hematopoietic lineage induced transcription and production of IL-6 by iSC cells. Lipopolysaccharide, tumor necrosis factor-alpha, IL-1 alpha, IL-6, and serum withdrawal induced iSC cell IL-6 mRNA. The kinetics of IL-6 production was confirmed in the mouse IL-6-dependent B9 bioassay and that activity could be neutralized with antisera to IL-6. Expression of both the IL-6 receptor and the gp130 signal transduction component by iSC as determined by northern analysis suggests an autocrine regulatory mechanism. The observed iSC production of IL-6 in vitro led to an investigation of the sciatic nerve crush model of Schwann cell activation in vivo. In the initial 12 h after crush injury, IL-6 message is induced. IL-6 mRNA expression was highest distal to the crush injury. Our in vitro data demonstrate that iSC cells produce IL-6 in response to PC12 cell coculture and to stimuli that induce IL-6 production in the hematopoietic lineage. The induction of IL-6 message distal to a crush injury suggests another mechanism by which Schwann cells facilitate peripheral nerve regeneration.
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