Antisense oligonucleotides to interleukin‐4 regulate IgE and IgG2a production by spleen cells from Nippostrongylus brasiliensis‐infected rats
- 1 March 1993
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 23 (3), 659-663
- https://doi.org/10.1002/eji.1830230313
Abstract
Interleukin-4 (IL-4) plays a key role in the regulation of immunoglobulin production. In the present study, we examined the role of IL-4 in the production of IgE and IgG2a by spleen cells from Nippostrongylus brasiliensis-infected rats using the antisense oligonucleotide strategy. Three antisense oligonucleotides (15 and 20 nucleotides) were selected near the ATG initiation codon of the murine IL-4 gene. Significant and reproducible inhibitions of IgE and IgG2a production were observed with the addition of two different oligonucleotides, the most inhibitory being specific for 15 nucleotides corresponding to the downstream AUG sequence oligodeoxynucleotide (ODN-1), while the corresponding sense sequence had no effect. The inhibition was directly related to the ODN-1 concentration on IgE response, and IgG2a production was more sensitive to the inhibitory effect of ODN-1 than the IgE response. Our results suggest that the ODN-1 effect is rather specific for the IL-4 gene since the production of other cytokines was not modified and the exogenous addition of IL-4 reversed the ODN-1 effect. In contrast to IgE and IgG2a, ODN-1 induced a significant enhancement of IgM synthesis. The use of a phosphorothioate ODN of the same sequence as ODN-1 resulted in a greater inhibitory effect on IgE and IgG2a production. These data indicate that IL-4 contributes to the spontaneous production of IgE and IgG2a, and argue that antisense strategy constitutes a useful tool for the regulation of antibody response.Keywords
This publication has 25 references indexed in Scilit:
- Tumour necrosis factor, IL-1 and IL-6 in bronchoalveolar washings and theirin vitroproduction duringNippostrongylus brasiliensisinfectionClinical and Experimental Immunology, 1992
- Molecular cloning of rat interleukin 4 cDNA and analysis of the cytokine repertoire of subsets of CD4+ T cellsEuropean Journal of Immunology, 1991
- Cytokines and lg switching: evolutionary divergence between mice and humansImmunology Today, 1990
- Infection with Nippostrongylus brasiliensis or injection of anti-IgD antibodies markedly enhances Fc-receptor-mediated interleukin 4 production by non-B, non-T cells.The Journal of Experimental Medicine, 1990
- Lymphokine Control of In Vivo Immunoglobulin Isotype SelectionAnnual Review of Immunology, 1990
- Il-4 Production By T Depleted Cells From Nippostrongylus Brasiliensis Infected MiceImmunological Investigations, 1989
- Specific inhibition of lymphokine biosynthesis and autocrine growth using antisense oligonucleotides in Th1 and Th2 helper T cell clones.The Journal of Experimental Medicine, 1988
- Sequence‐dependent hydrolysis of RNA using modified oligonucleotide splints and RNase HFEBS Letters, 1987
- Elevation of total serum IgE in rats following helminth parasite infectionNature, 1974
- IGE AND IGGA ANTIBODY-MEDIATED RELEASE OF HISTAMINE FROM RAT PERITONEAL CELLSThe Journal of Experimental Medicine, 1971