Soluble IL-6 Receptor Leads to a Paracrine Modulation of the IL-6-Induced Hepatic Acute Phase Response in Double Transgenic Mice

Malte Peters, Margarete Odenthal, Peter Schirmacher, Manfred Blessing, Elena Fattori, Gennaro Ciliberto, Karl Hermann Meyer Zum Büschenfelde, Stefan Rose-John

Research output: Contribution to journalArticle

Abstract

There is a growing number of soluble agonistic (IL-6, ciliary neurotropic factor, IL-11, and glia-derived neurotropic factor receptors) and antagonistic (IL-1 and TNF receptors) receptor proteins, modulating the biological functions of their cognate ligands. The physiologic role of these receptor molecules in vivo is unclear. In particular, it is not known how the specificity of function of soluble receptors after release into the blood stream is maintained. We addressed this question by studying the function of the soluble IL-6R (slL-6R) at the cellular level in the liver. We have generated double transgenic mice coexpressing human sIL-6R and human IL-6 in the liver and have analyzed the expression patterns by in situ hybridization. The expression of the human sIL-6R, driven by the phosphoenolpyruvate carboxykinase promoter, is located mainly in periportal areas, whereas human IL-6 under the control of the metallothionein promoter is uniformly expressed throughout the liver. We show here by in situ hybridization that acute phase protein gene expression induced by human IL-6 and human sIL-6R correlated with the periportal expression of sIL-6R, indicating that sIL-6R acts mainly in an area where it is generated. We conclude that in a concentration-dependent manner, at low concentrations of sIL-6R, there is a predominantly paracrine action at the site of its generation, whereas at higher concentrations of the sIL-6R there are both local and systemic effects.

Original languageEnglish
Pages (from-to)1474-1481
Number of pages8
JournalJournal of Immunology
Volume159
Issue number3
Publication statusPublished - Aug 1 1997

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Interleukin-6 Receptors
Acute-Phase Reaction
Transgenic Mice
Interleukin-6
Liver
In Situ Hybridization
Interleukin-11
Phosphoenolpyruvate
Interleukin-1 Receptors
Acute-Phase Proteins
Metallothionein
Tumor Necrosis Factor Receptors
Neuroglia
Ligands
Gene Expression
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Peters, M., Odenthal, M., Schirmacher, P., Blessing, M., Fattori, E., Ciliberto, G., ... Rose-John, S. (1997). Soluble IL-6 Receptor Leads to a Paracrine Modulation of the IL-6-Induced Hepatic Acute Phase Response in Double Transgenic Mice. Journal of Immunology, 159(3), 1474-1481.

Soluble IL-6 Receptor Leads to a Paracrine Modulation of the IL-6-Induced Hepatic Acute Phase Response in Double Transgenic Mice. / Peters, Malte; Odenthal, Margarete; Schirmacher, Peter; Blessing, Manfred; Fattori, Elena; Ciliberto, Gennaro; Meyer Zum Büschenfelde, Karl Hermann; Rose-John, Stefan.

In: Journal of Immunology, Vol. 159, No. 3, 01.08.1997, p. 1474-1481.

Research output: Contribution to journalArticle

Peters, M, Odenthal, M, Schirmacher, P, Blessing, M, Fattori, E, Ciliberto, G, Meyer Zum Büschenfelde, KH & Rose-John, S 1997, 'Soluble IL-6 Receptor Leads to a Paracrine Modulation of the IL-6-Induced Hepatic Acute Phase Response in Double Transgenic Mice', Journal of Immunology, vol. 159, no. 3, pp. 1474-1481.
Peters, Malte ; Odenthal, Margarete ; Schirmacher, Peter ; Blessing, Manfred ; Fattori, Elena ; Ciliberto, Gennaro ; Meyer Zum Büschenfelde, Karl Hermann ; Rose-John, Stefan. / Soluble IL-6 Receptor Leads to a Paracrine Modulation of the IL-6-Induced Hepatic Acute Phase Response in Double Transgenic Mice. In: Journal of Immunology. 1997 ; Vol. 159, No. 3. pp. 1474-1481.
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