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Complex of soluble human IL-6-receptor/IL-6 up-regulates expression of acute-phase proteins
Abstract
IL-6 is a major regulator of acute phase protein synthesis in the liver. It exerts its action via a plasma membrane receptor consisting of two subunits, a ligand binding 80-kDa glycoprotein and a 130-kDa glycoprotein involved in signal transduction. We genetically generated a soluble form of the 80-kDa subunit of the human IL-6R (shIL-6R) in mouse fibroblasts (NIH/3T3 cells). The shIL-6R added to human hepatoma cells (HepG2) amplified the induction of α1-antichymotrypsin and haptoglobin by IL-6 at the mRNA and protein level. Moreover, a model for a liver permanently exposed to high IL-6 concentrations has been developed; HepG2 cells were stably transfected with human IL-6-cDNA; 106 of the transfected cells (HepG2-IL-6) synthesized and secreted 2 micrograms of IL-6 within 24 h. Incubation of these cells with endogenous or exogenous IL-6 did not result in acute-phase protein induction. However, these IL-6-desensitized cells responded to other cytokines such as leukemia inhibitory factor, transforming growth factor β1, and IFN-γ, known to modulate acute phase protein synthesis in the liver. Incubation of HepG2-IL-6 cells with shIL-6R reconstituted their responsiveness to IL-6 in a dose- and time-dependent manner. The possible biologic role that might be played by the shIL-6R in disease is discussed.
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Self-citation
Metadata
- Authors
- Mackiewicz, A., Schooltink, H., Heinrich, P. C., & Rose-John, S.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1992-09
- Volume
- 149
- Issue
- 6
- Pages
- 2021-2027
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1488722235
- Cited by
- 370
- References
- 0
- FWCI
- 8.59
- Type
- journal article
- Language
- en
- Open access
- closed
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