Alternative splicing generates several interleukin-6 (IL-6) isoforms; for them an antagonistic activity to the wild-type IL-6 has been proposed. In this study we quantified the relative abundance of IL-6 mRNA isoforms in a panel of mouse tissues and in C2C12 cells during myoblast differentiation or after treatment with the Ca2+ ionophore A23187, the AMP-mimetic AICAR and TNF-alpha. The two mouse IL-6 isoforrns identified, IL-6 delta 5 (deletion of the first 58 bp of exon 5) and IL-6 delta 3 (lacking exon 3), were not conserved in rat and human, did not exhibit tissue specific regulation, were expressed at low levels and their abundance closely correlated to that of full-length IL-6. Species-specific features of the IL-6 sequence, such as the presence of competitive 3' acceptor site in exon 5 and insertion of retrotransposable elements in intron 3, could explain the production of IL-6 delta 5 and IL-6 delta 3. Our results argued against biological significance for mouse IL-6 isoforms.
The expression analysis of mouse interleukin-6 splice variants argued against their biological relevance
STOCCHI, VILBERTO
2012-01-01
Abstract
Alternative splicing generates several interleukin-6 (IL-6) isoforms; for them an antagonistic activity to the wild-type IL-6 has been proposed. In this study we quantified the relative abundance of IL-6 mRNA isoforms in a panel of mouse tissues and in C2C12 cells during myoblast differentiation or after treatment with the Ca2+ ionophore A23187, the AMP-mimetic AICAR and TNF-alpha. The two mouse IL-6 isoforrns identified, IL-6 delta 5 (deletion of the first 58 bp of exon 5) and IL-6 delta 3 (lacking exon 3), were not conserved in rat and human, did not exhibit tissue specific regulation, were expressed at low levels and their abundance closely correlated to that of full-length IL-6. Species-specific features of the IL-6 sequence, such as the presence of competitive 3' acceptor site in exon 5 and insertion of retrotransposable elements in intron 3, could explain the production of IL-6 delta 5 and IL-6 delta 3. Our results argued against biological significance for mouse IL-6 isoforms.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.