Characterization of two alternative Interleukin(IL)-10 5'UTR mRNA sequences, induced by lipopolysaccharide (LPS) stimulation of peripheral blood mononuclear cells.
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 degrees C for 24h, 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.
Forte
Giusi Irma
GI
Clinical Pathology, Section of General Pathology, Department of Pathobiology and Biomedical Methodology, University of Palermo, Italy.
Scola
Letizia
L
Bellavia
Daniele
D
Vaccarino
Loredana
L
Sanacore
Maria
M
Sisino
Giorgia
G
Scazzone
Concetta
C
Caruso
Calogero
C
Barbieri
Rainer
R
Lio
Domenico
D
D020121:5' Untranslated Regions; D001483:Base Sequence; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid
D020121:5' Untranslated Regions; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016753:Interleukin-10