TNF-alpha as an autocrine mediator and its role in the activation of Schwann cells.
In the peripheral nervous system (PNS), tumor necrosis factor-alpha (TNF-alpha) derived from activated Schwann cells (SCs) play a critical role as a pleiotropic mediator. In this study, we examined the function of TNF-alpha as an inflammatory mediator in SCs activation. TNF-alpha exhibits its biological effect through two distinct surface receptors, TNF receptor 1 (TNFR1) and TNFR2. We show here that cultured SCs express both TNFR1 and TNFR2, and that activation of these receptors by TNF-alpha promotes expression of TNF-alpha. Meanwhile, TNF-alpha also increased the production of other inflammatory mediators. Furthermore, TNF-alpha is involved in the induction of apoptosis through binding to TNFR in SCs. The activation of SCs by lipopolysaccharide (LPS) is partially mediated by SCs-derived TNF-alpha. These findings suggest the existence of a positive feedback loop in the activation of SC via TNF-alpha. This loop may be involved in the prolonged activation of SCs. Acute or chronic stimulation of TNF-alpha by SC at sites of PNS inflammation may be critical in determining whether TNF-alpha has activational, inflammatory, or cytotoxic effects on these cells.
Qin
Yongwei
Y
Key Laboratory for Neuroregeneration of JiangSu Province, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, PR China.
Cheng
Chun
C
Wang
Haibo
H
Shao
Xiaoyi
X
Gao
Yongjing
Y
Shen
Aiguo
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D019898:Autocrine Communication; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D051381:Rats; D017207:Rats, Sprague-Dawley; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000378:metabolism*; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D053148:Caspase 3