Role of IL-6 and the Soluble IL-6 Receptor in Inhibition of VCAM-1 Gene Expression
| Autor: | Jae-Wook Oh, Nicholas J. Van Wagoner, Stefan Rose-John, Etty N. Benveniste |
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| Rok vydání: | 1998 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 161:4992-4999 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Adhesion molecules such as VCAM-1 and ICAM-1 are increased in the central nervous system (CNS) during inflammatory responses and contribute to extravasation of leukocytes across the blood-brain barrier (BBB) and into CNS parenchyma. Astrocytes contribute to the structural integrity of the BBB and can be induced to express VCAM-1 and ICAM-1 in response to cytokines such as TNF-α, IL-1β, and IFN-γ. In this study, we investigated the influence of IL-6 on astroglial adhesion molecule expression. IL-6, the soluble form of the IL-6R (sIL-6R), or both IL-6 plus sIL-6R, had no effect on VCAM-1 or ICAM-1 gene expression. Interestingly, the IL-6/sIL-6R complex inhibited TNF-α-induced VCAM-1 gene expression but did not affect TNF-α-induced ICAM-1 expression. The inhibitory effect of IL-6/sIL-6R complex was reversed by the inclusion of anti-IL-6R and gp130 Abs, demonstrating the specificity of the response. A highly active fusion protein of sIL-6R and IL-6, covalently linked by a flexible peptide, which is designated H-IL-6, also inhibited TNF-α-induced VCAM-1 expression. sIL-6R alone was an effective inhibitor of TNF-α-induced VCAM-1 due to endogenous IL-6 production. These results indicate that the IL-6 system has an unexpected negative effect on adhesion molecule expression in glial cells and may function as an immunosuppressive cytokine within the CNS. |
| Databáze: | OpenAIRE |
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