Expression of interleukin-6 receptor (IL-6R) and gp130 mRNA in PC12 cells and sympathetic neurons: modulation by tumor necrosis factor alpha (TNF-alpha).
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 alpha (TNF-alpha) 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-alpha. The stimulatory effect of TNF-alpha 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.
März
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Department of Physiology, University of Basel, Switzerland.
Gadient
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Otten
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D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D050822:Cytokine Receptor gp130; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000235:genetics*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018123:Receptors, Interleukin / Q000235:genetics*; D019947:Receptors, Interleukin-6; D015398:Signal Transduction; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D015703:Antigens, CD; D005938:Glucocorticoids; C494201:Il6st protein, rat; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D050822:Cytokine Receptor gp130; D003907:Dexamethasone