Characterization of two alternative Interleukin(IL)-10 5_UTR mRNA sequences, induced by lipopolysaccharide (LPS) stimulation of peripheral blood mononuclear cells

Abstract

IL-10 production shows a broad-spectrum of individual response, suggesting a genetic component of approximately 75%. Different polymorphisms located close to, or within the IL-10 gene has been demonstrated to influence its transcription rate whereas the post-transcriptional regulation of IL-10 production has not well elucidated. The main responsible elements at this control level are both the 5′- and 3′-untranslated regions (UTR's) of mRNAs, and as the 3′-UTR regions are mainly involved in the stability and decay rate of mRNAs, the 5′-UTR regions mediate the binding rate of the molecule with ribosomal 40S subunit as a cis-acting element. Herein are report data on the identification of two IL10 mRNA that differ by the length of respective 5′UTR regions (160 and 288 nucleotides, respectively; EMBL accession nrs: EU751618 and EU751619) produced after stimulation of human blood samples with bacterial lipopolysaccharide (LPS). The longer 5′UTR is constitutively expressed in unstimulated PBMC cells cultured at 37 °C for 24 h, while in LPS stimulated cells an additional IL-10 mRNA molecule, containing a shorter 5′UTR, is synthesized. RNADRAW software (http://www.rnadraw.com/) analysis have indicated that the secondary structures of the shorter 5′UTR IL-10 mRNA region is more available for the binding to the 40S ribosomal subunit. In conclusion, our data seem to suggest that LPS could influence the post-transcriptional control of IL-10 production inducing an alternative mRNA immediately available in response to the inflammatory stimulation.