Transcription of the IL10 gene reveals allele-specific regulation at the mRNA level

Abstract

Interleukin-10 (IL10) is a cytokine with key regulatory and anti-inflammatory function involved in the pathogenesis of various diseases. Although the large interindividual differences in the production of IL10 have been extensively associated with polymorphisms and haplotypes of the IL10 gene, surprisingly little evidence exists that this variation is actually dictated by IL10 haplotypes. Using the technique of allele-specific transcript quantification, the ratio between two alleles (A and G) of the IL10 gene was characterized in 15 healthy heterozygous individuals. Two groups were identified whereby donors in group 1 exhibited a 1 : 1 ratio, whereas those in group 2 exhibited a ratio>1 (P<0.0017). We found that donors heterozygous for haplotype IL10.2 (one of the four ancient IL10 haplotypes) were only prevalent in the group that showed higher allelic expression ratios. In this study we show that IL10 alleles are indeed differentially transcribed in cells from heterozygous individuals and that IL10 haplotypes dictate production of IL10. These findings show that interindividual differences in IL10 protein levels can be explained at the transcriptional level.

The Correlation Between IL-1β and IL-10 Levels in Estimating The Risk of Febrile Seizures

“…In the present study, IL-1β/IL-10 plasma levels were significantly correlated to febrile seizures (Table 5; r=0.573; p<0.05) These inflammation cytokine (IL-1β) and anti-inflammation cytokine (IL-10) ratio correlation was inconsistent with [16] findings, but [11] study used IL-1β as an inflammation cytokine and IL-1RA as an anti-inflammation cytokine [16].…”

“…Dube et al (2000) [8] showed high doses of IL-1β are sufficient to generate seizures even without increased brain temperature [8,9]. There is an evidence of serial treatment of cells with LPS and ATP provides a very powerful stimulus to induce rapid and efficient release of IL-1β from monocytes, macro-phages and dendritic cells [10,11]. Research carried out by [5] found elevated levels of IL-1β in patients with febrile seizures when compared to normal ones, febrile patients without seizures and status epilepticus [5].…”

Characteristics of rapid vs slow progression to type 1 diabetes in multiple islet autoantibody-positive children

“…In addition to IL2 and CD25, several other loci associated with human type 1 diabetes encode molecules that play a role in the immune regulation of T cell-mediated adaptive immune responses, or of inflammatory signals provided by the innate immune system [30]. These include IL-10 [16,37], IFIH1 [38,39], IL18RAP [40] and PTPN22 [41], which were able to stratify progression in our study. Although a number of type 1 diabetes-associated gene SNPs did not significantly add to the discrimination between the rapid and slow progressors (i.e.…”

Posttranscriptional regulation of interleukin-10 expression by hsa-miR-106a

“…Half life of IL10 mRNA in normal melanocytes is much shorter than in melanoma cell lines (7). Also, genetic variations in the 3Ј UTR of IL10 have been shown to be associated with IL-10 levels that could lead to disease pathogenesis (8,9). Therefore, a pellucid understanding of the posttranscriptional regulation of IL10 will be of scientific and clinical significance.…”