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

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.