Interleukin-6 production by Schwann cells and induction in sciatic nerve injury.
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.
Bolin
L M
LM
DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304-1104.
Verity
A N
AN
Silver
J E
JE
Shooter
E M
EM
Abrams
J S
JS
D000818:Animals; D015703:Antigens, CD; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000494:pharmacology; D003584:Cytological Techniques; D015850:Interleukin-6 / Q000096:biosynthesis*; D008562:Membrane Glycoproteins / Q000235:genetics; D009409:Nerve Crush; D016716:PC12 Cells; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D019947:Receptors, Interleukin-6; D012583:Schwann Cells / Q000378:metabolism*; D012584:Sciatic Nerve / Q000293:injuries* / Q000378:metabolism; D015398:Signal Transduction; D014949:Wounds, Nonpenetrating / Q000378:metabolism*
D015703:Antigens, CD; D016207:Cytokines; C494201:Il6st protein, rat; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130