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Double-stranded RNA regulates IL-4 expression
K E Kehoe1, M A Brown, F Imani
1Division of Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Asthma and Allergy Center, Baltimore, MD 21224, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|August 18, 2001
Summary
Double-stranded RNA (dsRNA) can induce T-helper 2 (Th2) immune responses by activating NF-AT in human lymphocytes. Low dsRNA concentrations promote IL-4 expression, potentially hindering optimal anti-viral immunity.
Area of Science:
- Immunology
- Molecular Biology
- Virology
Background:
- Double-stranded RNA (dsRNA) is a key molecular pattern associated with viral infections.
- Viral infections typically elicit strong T-helper 1 (Th1) immune responses, but T-helper 2 (Th2) responses are also observed.
Purpose of the Study:
- To investigate the effects of dsRNA on the induction of Th2 responses in human lymphocytes.
- To determine if dsRNA can directly influence the expression of the Th2 cytokine Interleukin-4 (IL-4).
Main Methods:
- Treatment of human lymphocytes with varying concentrations of dsRNA.
- Analysis of cytokine expression, specifically IL-4.
- Assessment of nuclear factor activation (NF-kappaB, NF-AT1, NF-AT2).
- Reporter gene assays using IL-4 promoter-driven chloramphenicol acetyltransferase in transfected Jurkat cells.
Main Results:
- Low concentrations of dsRNA (0.1-1 microg/ml) induced the expression of IL-4 in human lymphocytes.
- dsRNA treatment led to concentration-dependent activation of NF-kappaB and NF-AT2, but not NF-AT1.
- dsRNA directly activated an IL-4 promoter in reporter gene assays, demonstrating a non-TCR-associated NF-AT activation pathway.
Conclusions:
- dsRNA can act as a non-TCR-associated activator of NF-AT in human cells, directly influencing IL-4 gene expression.
- Low concentrations of dsRNA in vivo may promote Th2-dominant responses.
- These Th2 responses might not be optimal for protective immunity against viral infections.