Here, we demonstrate that the histone deacetylase inhibitor, trichostatin A, significantly down-regulated CD154 and IL-10 and up-regulated IFN-gamma gene expression in SLE T cells.
Here, we discuss the role of IL-10 in autoimmune diseases and examine its beneficial effects in cellular-based autoimmune diseases such as multiple sclerosis (MS) or its involvement in humoral-based autoimmune diseases such as systemic lupus erythematosus (SLE).
Associations have been reported between single nucleotide polymorphisms (SNPs) of IL-10 and the Ile50Val polymorphism of the IL-4 receptor gene (IL-4R) gene and atopy and autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis.
Gain of IL-10 proinflammatory functions may contribute to its pathogenic role in autoimmune diseases characterized by elevated type I IFN levels, such as systemic lupus erythematosus.
In the study population no significant associations of individual IL10.R and G alleles or their haplotypes with susceptibility to SLE or major clinical manifestations were observed.
We found that the homozygous non-ht1 combined with short allele (CA repeat number < or =21) of IL10.G has a dose-dependent effect on SLE susceptibility: non-ht1/non-ht1 with homozygous short allele showed a higher OR (OR=4.11, 95% CI: 1.27-13.2, P=0.018) of association with SLE than the genotype of non-ht1/non-ht1 with heterozygous short/long allele (OR=2.98, 95% CI: 1.26-7.07, P=0.013) and homozygous long allele (OR=1.05, 95% CI: 0.62-1.78, P=0.848).
We found that the homozygous non-ht1 combined with short allele (CA repeat number < or =21) of IL10.G has a dose-dependent effect on SLE susceptibility: non-ht1/non-ht1 with homozygous short allele showed a higher OR (OR=4.11, 95% CI: 1.27-13.2, P=0.018) of association with SLE than the genotype of non-ht1/non-ht1 with heterozygous short/long allele (OR=2.98, 95% CI: 1.26-7.07, P=0.013) and homozygous long allele (OR=1.05, 95% CI: 0.62-1.78, P=0.848).
The IL10 meta-analysis showed a significant association between SLE and the G11 allele of IL10.G (OR=1.279, 95% CI; 1.027-1.593, P=0.028) in whole populations, and IL10 promoter -1082G allele was associated with SLE in Asians (OR=1.358, 95% CI; 1.015-1.816, P=0.039).
IL10/TNFalpha interaction influences susceptibility to DLE and the appearance of specific autoantibodies in SLE patients, whereas high TNFalpha producer genotypes represent a significant risk factor for SLE.
The objective of this study was to evaluate the genetic profiles of selected cytokines (transforming growth factor beta 1, tumor necrosis factor alpha, interleukin-6, interferon gamma, and interleukin-10) in systemic lupus erythematosus and the contributions of human leukocyte antigen (HLA)-DRB1 and -DQB1 alleles to susceptibility for this disease.
Among identified SNPs, the rare C allele of IL10-592A-->C was significantly associated with the SDI among SLE patients in the following three alternative models: codominant (P = 0.007, odds ratio = 1.70), dominant (P = 0.02, odds ratio = 1.85) and recessive (P = 0.05, odds ratio = 2.25).
To this end, TNFalpha serum levels were quantified in 171 SLE patients and 215 healthy controls by ELISA techniques and polymorphisms at positions -1,082 and -308 of the IL-10 and TNFalpha gene promoters were determined by PCR amplification followed by hybridization with fluorescent-labeled allele-specific probes in 192 SLE patients and 343 matched controls.