Expression of interleukin-6 receptor (IL-6R) and gp130 mRNA in PC12 cells and sympathetic neurons: modulation by tumor necrosis factor α (TNF-α)

• Published in: Brain research 1996-01, Vol.706 (1), p.71-79
• Main Authors: März, P., Gadient, R.A., Otten, U.
• Format: Article
• Language: English
• Subjects: Animals; Antigens, CD - genetics; Biological and medical sciences; c- fos; Cell Differentiation - drug effects; Cell receptors; Cell structures and functions; Cells, Cultured; Cytokine Receptor gp130; Dexamethasone - pharmacology; Differentiation; Fundamental and applied biological sciences. Psychology; Glucocorticoid; Glucocorticoids - pharmacology; Gp 130; Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors; Hybridization, in situ; In Situ Hybridization; Interleukin-6 receptor; Membrane Glycoproteins - genetics; Molecular and cellular biology; Neurons - drug effects; Neurons - metabolism; PC12 cell; PC12 Cells; Rats; Rats, Sprague-Dawley; Receptors, Interleukin - genetics; Receptors, Interleukin-6; Reverse transcriptase-polymerase chain reaction; RNA, Messenger - biosynthesis; RNA, Messenger - drug effects; Signal Transduction; Superior Cervical Ganglion - cytology; Superior Cervical Ganglion - drug effects; Superior Cervical Ganglion - metabolism; Sympathetic neuron; Tumor necrosis factor o; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/0006-8993(95)01210-9

Recent findings indicate that IL-6, besides its various biological effects, also exerts neurotrophic and neuroprotective functions. Using the pheochromocytoma cell line PC12 and cultured primary sympathetic neurons, we investigated whether neurons express the IL-6 receptors, IL-6R and gp130, and how they might be regulated. For these studies we used RT-PCR and in situ hybridization. We provide here evidence for the expression of functional IL-6Rs in peripheral sympathetic neurons and PC12 cells. Furthermore we demonstrate that cytokines modulate the expression of IL-6R and gp130 mRNA. This modulation is much more pronounced in neuronally-differentiated PC12 cells than in undifferentiated cells. Among various cytokines tested, tumor necrosis factor α (TNF-α) turned out to be a major regulator of the IL-6R and gp130 mRNA expression. The induction was time- and dose-dependent for both genes. Maximal induction was reached within 16 h at a concentration of 0.1 nM TNF-α. The stimulatory effect of TNF-α on the IL-6R system was completely inhibited by the simultaneous addition of the glucocorticoid dexamethasone. In summary, our results show that sympathetic neurons and neuron-like differentiated PC12 cells express functional IL-6R and gp130, and that the expression of their mRNAs is modulated by cytokines. We suggest that cytokines such as IL-6 can modulate sympathetic neuron function.