Inhibition of IgE production by epsilon (ϵ) chain-specific antisense oligonucleotides (AOs) studied on human myeloma cell line U266 and peripheral blood mononuclear cells of a patient with hypereosinophilia

The biosynthesis of interleukin-6 receptor (IL-6R) and gp130 in vitro was blocked using specific antisense oligonucleotides (ASO) in HepG2 liver cells and the efficacy of various ASOs was tested on the generation of IL-6-induced junB mRNA. We used three ASOs specific for the IL-6 receptor, three specific for gp130 and a control (nonsense) oligonucleotide specific for epsilon-chain of IgE (not expressing in HepG2 cells). Our data indicate that a gp130-specific ASO, g2, was the most effective blocker of IL-6-induced junB mRNA, whilst the IL-6 receptor ASOs alone were ineffective. The mechanism of gene inactivation by ASO treatment was partially elucidated by demonstration of the loss of gp130 mRNA from cells treated with ASOs showing functional efficacy. Our data may help to design antisense oligonucleotides that are effective in therapy (e.g. as anti-inflammatory agents) in the future.

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Gp130‐specific Antisense Oligonucleotides Inhibit Il‐6 Signal Inducing Junb Mrna Transcription in the Human Hepatoma Cell Line, Hepg2

Varga

Fülöp

Holub

et al. 2001

Cell Biology International

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Antisense strategies: functions and applications in immunology

et al. 1999

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Prospects for a Vaccine in Allergic Diseases and Asthma

2000

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Allergen-specific immunotherapy is widely used to treat allergic diseases, and current research is now focusing on the development of therapeutic vaccines acting on the IgE immune response following allergen challenge. The IgE immune response is dependent on genetic and environmental factors; production of IgE results from complex interactions among B cells, T cells, mast cells, basophils,surface and adhesion molecules and various cytokines. New vaccination methods under investigation involve allergen-specific or nonspecific methodology. Allergen-specific methods currently being developed include allergoids, passive saturation of effector cells, plasmid DNA immunisation and antigen-antibody complexes. The mechanisms of immunotherapy using allergen-specific methods differ with the allergens and the route of immunisation used (parenteral, intranasal, sublingual, oral or bronchial). Many vaccines being developed at present comprise synthetic, recombinant or highly purified subunit antigens, which although they have increased safety may also be less immunogenic.It is hoped that the addition of adjuvants will overcome this drawback. Methods of increasing the dose of allergen while reducing the possibility of an anaphylactic reaction include the use of non-anaphylactic isoforms of the allergens, alteration of the tertiary structure of the allergens and construction of minimal allergen-derived T cell peptides. Nonspecific approaches include humanised anti-IgE antibodies,moderation of the T(H)2 cytokine network and antisense oligodeoxynucleotide therapy.

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Inhibition of IgE production by epsilon (ϵ) chain-specific antisense oligonucleotides (AOs) studied on human myeloma cell line U266 and peripheral blood mononuclear cells of a patient with hypereosinophilia

Cited by 3 publications

References 14 publications

Gp130‐specific Antisense Oligonucleotides Inhibit Il‐6 Signal Inducing Junb Mrna Transcription in the Human Hepatoma Cell Line, Hepg2

Gp130‐specific Antisense Oligonucleotides Inhibit Il‐6 Signal Inducing Junb Mrna Transcription in the Human Hepatoma Cell Line, Hepg2

Antisense strategies: functions and applications in immunology

Prospects for a Vaccine in Allergic Diseases and Asthma

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