Induction of neuronal differentiation in PC12 cells by B-cell stimulatory factor 2/interleukin 6.

Satoh, T; Nakamura, S; Taga, Tetsuya; Matsuda, Tadashi; Hirano, Toshio; Kishimoto, T; Kaziro, Y

doi:10.1128/mcb.8.8.3546

Cited by 361 publications

(152 citation statements)

References 13 publications

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“…IL-6 has been shown to have beneficial potential in the CNS because of its neurotrophic and neuroprotective effects (Satoh et al, 1988;Hama et al, 1989;Gadient and Otten, 1997;Loddick et al, 1998;März et al, 1998b), and anti-inflammatory actions through the inhibition of VCAM-1, intercellular adhesion molecule-1, and TNF-␣ expression by CNS cells Shrikant et al, 1995;Oh et al, 1998). However, other reports suggest that IL-6 is detrimental and adds to the pathophysiology associated with CNS disorders (Campbell et al, 1993;Klein et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6 (IL-6) Production by Astrocytes: Autocrine Regulation by IL-6 and the Soluble IL-6 Receptor

et al. 1999

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In the CNS, astrocytes are a major inducible source of interleukin-6 (IL-6). Although IL-6 has beneficial effects in the CNS because of its neurotrophic properties, its overexpression is generally detrimental, adding to the pathophysiology associated with CNS disorders. Many factors have been shown to induce IL-6 expression by astrocytes, particularly the cytokines tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β). However, the role of IL-6 in its own regulation in astrocytes has not been determined. In this study, we examined the influence of IL-6 alone or in combination with TNF-α or IL-1β on IL-6 expression. IL-6 alone had no effect on IL-6 expression; however, the addition of the soluble IL-6 receptor (sIL-6R) induced IL-6 transcripts. Addition of TNF-α or IL-1β plus IL-6/sIL-6R led to synergistic increases in IL-6 expression. This synergy also occurred in the absence of exogenously added IL-6, attributable to TNF-α- or IL-1β-induced endogenous IL-6 protein production. IL-6 upregulation seen in the presence of TNF-α or IL-1β plus IL-6/sIL-6R was transcriptional, based on nuclear run-on analysis. Experiments were extended to other IL-6 family members to determine their role in IL-6 regulation in astrocytes. Oncostatin M (OSM) induced IL-6 alone and synergized with TNF-α for enhanced expression. These results demonstrate that IL-6/sIL-6R and OSM play an important role in the regulation of IL-6 expression within the CNS, particularly in conjunction with the proinflammatory cytokines TNF-α and IL-1β.

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Section: Discussionmentioning

confidence: 99%

Interleukin-6 (IL-6) Production by Astrocytes: Autocrine Regulation by IL-6 and the Soluble IL-6 Receptor

et al. 1999

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“…It was proposed on the basis of these results that a sustained activation of the MAP kinase cascade might be required for the differentiation of PC12 cells [15,16]. If such a phenomenon is central to the differentiation response then it should also apply to other agents which promote PC12 cell differentiation, including CAMP analogues such as dibutyryl cyclicAMP [18], interleukin 6 [19] and fibroblast growth factors [l&20]. As CAMP is well known to activate the CAMP-dependent protein kinase and had not previously been reported to regulate the activity of MAP kinase, we examined whether a more membrane permeant CAMP analogue, S-(4-chlorophenylthio)-cyclicAMP (CPT-CAMP) would promote PC12…”

Section: Introductionmentioning

confidence: 99%

Differentiation of PC12 cells in response to a cAMP analogue is accompanied by sustained activation of mitogen‐activated protein kinase

1994

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It has been proposed previously that the sustained activation of mitogen-activated protein kinase may be necessary for the differentiation of PC12 cells. Differentiation of PC12 cells is induced by many extracellular agonists including nerve growth factor (NGF) and cyclicAMP analogues, but not epidennal growth factor (EGF), insulin or phorbol esters. Our results demonstrate that: (i) 8-(4-chlorophenylthio)-cyclicAMP (CPT-CAMP) activates MAP kinase; this raises the possibility that the MAP kinase pathway may be activated by agents that act through adenylate cyclase; (ii) NGF and UT-CAMP as well as phorbol esters promote sustained activation of MAP kinase. This suggests that while sustained MAP kinase activation may be associated with differentiation it may not be sufficient, and that other as yet unidentified parallel pathways may be involved.

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“…On hepatocytes IL-6 is a transcriptional inducer of a large group of plasma proteins, including C-reactive protein, al-acid glycoprotein, haptoglobin, hemopexin, fibrinogen, etc., which are also known as acute phase proteins or reactants [2]. IL-6, however, is also involved in the differentiation of T-cells [3] and neurons [4]. Besides the physiological activities of IL-6, deregulation of the expression of this cytokine has been postulated to be responsible for the development of several…”

mentioning

confidence: 99%

Single‐step purification and structural characterization of human interleukin‐6 produced in Esherichia coli From a T7 RNA polymerase expression vector

Arcone

Pucci²,

Zappacosta³

et al. 1991

European Journal of Biochemistry

130

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Human interleukin-6 or B-cell stimulatory factor-2 is a cytokine involved in acute phase and immune response. Cloning of cDNA for human interleukin-6 in the pT7.7 expression plasmid under the control of a bacteriophage T7 RNA polymerase promoter system allows rapid production of the cytokine in Escherichiu coli. Upon cell induction with isopropyl thiogalactopyranoside, recombinant human interleukin-6 is overexpressed and forms insoluble inclusion bodies. Solubilization of the protein with 6 M guanidine hydrochloride and refolding in the presence of a reduction/oxidation system results in a quantitative recovery of recombinant human interleukin-6. This material is already 70% pure and can be further purified to homogeneity with a single passage over a weak anionic-exchange column. Eytended structural Characterization of the purified protein by electrospray mass spectrometry, automated Edman degradation and peptide mapping by high-pressure liquid chromatography/fastatom-bombardment mass spectrometry demonstrates that recombinant human interleukin-6 is identical to the natural protein both in amino acid sequence and S-S bridge content. However, it contains a minor component accounting for about 20% of the entire translated protein which exhibits a Met-Ala dipeptide extension at the Nterminus. Purified recombinant human interleukin-6 is biologically active because it is able to induce at least 70-fold the human C-reactive promoter transfected in human hepatoma Hep 3B cells and is stable for several months in 10% glycerol at 4°C. The expression system described in the present work has the main advantage of producing a high yield of recombinant human interleukin-6 (about 25 mg/l) combined with a very simple purification scheme.Interleukin-6 (IL-6) or B-cell stimulatory factor 2, is a major cytokine which has been shown to play a central role in the physiology of several tissues and organs [l]. The main targets of IL-6 are the immune system and the liver [l, 21. On B cells IL-6 induces the growth of hybridomas and plasmacytomas, the expression of class I antigens and the production and secretion of immunoglobulins [l]. On hepatocytes IL-6 is a transcriptional inducer of a large group of plasma proteins, including C-reactive protein, al-acid glycoprotein, haptoglobin, hemopexin, fibrinogen, etc., which are also known as acute phase proteins or reactants [2]. IL-6, however, is also involved in the differentiation of T-cells [3] and neurons [4]. Besides the physiological activities of IL-6, deregulation of the expression of this cytokine has been postulated to be responsible for the development of several

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Induction of neuronal differentiation in PC12 cells by B-cell stimulatory factor 2/interleukin 6.

Cited by 361 publications

References 13 publications

Interleukin-6 (IL-6) Production by Astrocytes: Autocrine Regulation by IL-6 and the Soluble IL-6 Receptor

Interleukin-6 (IL-6) Production by Astrocytes: Autocrine Regulation by IL-6 and the Soluble IL-6 Receptor

Differentiation of PC12 cells in response to a cAMP analogue is accompanied by sustained activation of mitogen‐activated protein kinase

Single‐step purification and structural characterization of human interleukin‐6 produced in Esherichia coli From a T7 RNA polymerase expression vector

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