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IL-17 reduces TNF-induced Rantes and VCAM-1 expression
Bruno Schnyder1, Silvia Schnyder-Candrian, Andreas Pansky
1Biomedical Research Foundation (SBF), Lauchefeld 31, CH-9548 Matzingen, Switzerland. schnyder@cnrs-orleans.fr
Cytokine
|June 25, 2005
Summary
Interleukin-17 (IL-17) exhibits dual functions, inhibiting Rantes and stimulating IL-6 via the IL-17 receptor (IL-17R). These activities display different potencies and sensitivities to IL-17R antagonism, revealing functional diversity.
Area of Science:
- Immunology
- Cell Biology
Background:
- Memory T cells produce Interleukin-17 (IL-17), a cytokine with diverse biological roles.
- The functional diversity of IL-17, particularly its receptor-level interactions, remains incompletely understood.
Purpose of the Study:
- To investigate the functional diversity of IL-17 at the receptor level.
- To compare the inhibitory and stimulatory activities of IL-17 and their dependence on the IL-17 receptor (IL-17R).
Main Methods:
- Assessed IL-17's effects on Rantes and IL-6 expression in human and mouse fibroblasts.
- Utilized an IL-17R-neutralizing antibody (M202) and IL-17R gene-deficient mice.
- Quantified dose-response relationships (IC50, ED50) and NF-kappaB pathway involvement.
Main Results:
- IL-17 potently inhibited TNF-induced Rantes expression (IC50=0.2 ng/ml) and stimulated IL-6 secretion (ED50=1.2 ng/ml).
- IL-17R neutralization reversed IL-6 upregulation but only partially affected Rantes inhibition.
- IL-17R was essential for Rantes inhibition, as demonstrated in IL-17R gene-deficient mice.
Conclusions:
- Both inhibitory (Rantes) and stimulatory (IL-6) functions of IL-17 involve the IL-17 receptor.
- Distinct dose-responses and differential sensitivities to IL-17R antagonism highlight the functional divergence of IL-17 signaling pathways.