The role and molecular mechanisms of alternative splicing of Th2-cytokines IL-4 and IL-5 in atopic bronchial asthma

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Abstract

Bronchial asthma (BA) is a heterogeneous chronic inflammatory disease of the respiratory tract. Allergic asthma is the most common (up to 80% of cases) phenotype developing through Th2-dependent mechanisms involving cytokines: IL-4, IL-5, IL-9 and IL-13. The genes encoding Th2-cytokines have a mosaic structure (encode exons and introns). Therefore, several mature mRNA transcripts and protein isoforms can be derived from a single mRNA precursor through alternative splicing, and they may contribute to BA pathogenesis. Analysis of published studies and databases revealed the existence of alternative mRNA transcripts for IL-4, IL-5, and IL-13. Alternative transcripts of IL-4 and IL-5 carry open reading frames and therefore can encode functional proteins. It was shown that not only alternative mRNA transcripts are exist for IL-4, but alternative protein isoforms, as well. Natural protein isoform IL-4δ2 lacking part encoded by exon-2 was identified. Similarly, alternative mRNA transcript omitting exon-2 (IL-5δ2) was also identified for IL-5. In this review, we summarize current knowledge about identified alternative mRNA transcripts and protein isoforms of Th2-cytokinins, first of all IL-4 and IL-5. We have analyzed biological properties of alternative variants of these cytokines, their possible role in the allergic asthma pathogenesis, and considered their diagnostic and therapeutic potential.

About the authors

I. P Shilovskiy

Institute of Immunology, National Research Center, Federal Medical-Biological Agency Russia

Email: ip.shilovsky@nrcii.ru
115522 Moscow, Russia

V. I Kovchina

Institute of Immunology, National Research Center, Federal Medical-Biological Agency Russia

115522 Moscow, Russia

E. D Timotievich

Institute of Immunology, National Research Center, Federal Medical-Biological Agency Russia

115522 Moscow, Russia

A. A Nikolskii

Institute of Immunology, National Research Center, Federal Medical-Biological Agency Russia

115522 Moscow, Russia

M. R Khaitov

Institute of Immunology, National Research Center, Federal Medical-Biological Agency Russia;Federal State Autonomous Educational Institution of Higher Education “N. I. Pirogov Russian National Research Medical University” of the Ministry of Health of the Russian Federation

115522 Moscow, Russia;117997 Moscow, Russia

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