Role and Molecular Mechanisms of Alternative Splicing of Th2-Cytokines IL-4 and IL-5 in Atopic Bronchial Asthma.

Autor: Shilovskiy IP; National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, 115522, Russia. ip.shilovsky@nrcii.ru., Kovchina VI; National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, 115522, Russia., Timotievich ED; National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, 115522, Russia., Nikolskii AA; National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, 115522, Russia., Khaitov MR; National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, 115522, Russia.; Pirogov Russian National Research Medical University, Ministry of Health of the Russian Federation, Moscow, 117997, Russia.
Jazyk: angličtina
Zdroj: Biochemistry. Biokhimiia [Biochemistry (Mosc)] 2023 Oct; Vol. 88 (10), pp. 1608-1621.
DOI: 10.1134/S0006297923100152
Abstrakt: Bronchial asthma (BA) is a heterogeneous chronic inflammatory disease of the respiratory tract. Allergic (atopic) asthma is the most common (up to 80% of cases) phenotype developing through the 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 the published studies and databases revealed existence of the alternative mRNA transcripts for IL-4, IL-5, and IL-13. The 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 exist for IL-4, but alternative protein isoforms, as well. Natural protein isoform (IL-4δ2) lacking the part encoded by exon-2 was identified. Similarly, alternative mRNA transcript with deleted exon-2 (IL-5δ2) was also identified for IL-5. In this review, we summarize current knowledge about the identified alternative mRNA transcripts and protein isoforms of Th2-cytokinins, first of all IL-4 and IL-5. We have analyzed biological properties of the alternative variants of these cytokines, their possible role in the allergic asthma pathogenesis, and considered their diagnostic and therapeutic potential.
Databáze: MEDLINE
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