Association of Cytokine Polymorphic Inheritance and in Vitro Cytokine Production in Anti-Cd3/Cd28-Stimulated Peripheral Blood Lymphocytes1

Hoffmann, Steven C.; Stanley, Eran M.; Cox, Elizabeth; Craighead, Nancy; Dimercurio, Barbara S.; Koziol, Deloris E.; Harlan, David M.; Kirk, Allan D.; Blair, Patrick J.

doi:10.1097/00007890-200110270-00019

Cited by 310 publications

(254 citation statements)

References 39 publications

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“…Using purified monocytes ( Figure 1) and B cells (Figure 3), our results support the concept that individuals with the C allele both spontaneously and upon LPS stimulation produce higher levels of IL-10 as compared to individuals with the A allele in these cell types. Others have reported a similar phenomena using PBMCs and Con A, anti-CD3/CD28 or interferon-α as a stimulus [17,29,35,36]. Though not statistically significant, a slight increase in IL-10 production was observed in purified T cells from individuals with the C allele when stimulated with either PMA/ionomycin or anti-CD3/CD28 (Figure 2).…”

Section: Discussionsupporting

confidence: 55%

“…Many of these studies have relied on whole cell blood cultures or partially purified peripheral blood mononuclear cells stimulated with lipopolysaccharide to observe this effect [27,28]. Others have used purified T cells and stimulated with concanavalin A or anti-CD3/CD28 with mixed results in terms of IL-10 production [17,29]. In the present study, we analyzed IL-10 production from highly enriched populations of T cells, B cells and monocytes under various stimulation conditions in individuals either homozygous for the C or A allele at position -571 of the IL-10 promoter.…”

Section: Introductionmentioning

confidence: 99%

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Differential interleukin-10 production stratified by −571 promoter polymorphism in purified human immune cells

Steinke¹,

Barekzi²,

Huyett³

et al. 2007

Cellular Immunology

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SummaryA C-to-A base substitution has been identified at bp -571 in the IL-10 promoter and has been linked to numerous diseases. To investigate the role of this polymorphism on IL-10 production, T cells, B cells and monocytes were enriched from peripheral blood from subjects either homozygous for the C or A allele. Treatment of monocytes and B cells with lipopolysaccharide from individuals homozygous for the C allele resulted in higher levels of IL-10 production as compared to monocytes from individuals homozygous for the A allele. Though not statistically significant, when B cells were treated with anti-IgM or T cells with concanavalin A higher levels of IL-10 were produced from individuals homozygous for the A allele. Changes in IL-10 protein production were paralleled by similar changes in IL-10 mRNA production. These results demonstrate that changes in IL-10 production observed due to the -571 genotype depend on both cell type and stimulus.

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Section: Discussionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Differential interleukin-10 production stratified by −571 promoter polymorphism in purified human immune cells

Steinke¹,

Barekzi²,

Huyett³

et al. 2007

Cellular Immunology

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“…These results are in concordance with data presented in a study on stimulated purified blood lymphocytes. 40 In this study, it was shown that the production of IL-10 was larger for subjects with the G allele compared with subjects with the A allele. Mö rmann et al 25 also found that the G allele was associated with a higher IL-10 production in mononuclear cells after LPS stimulation.…”

Section: Discussionmentioning

confidence: 61%

“…19,[25][26][27]32,40,41 Thus, Turner et al 27 found that subjects who were negative for the A allele exhibited a higher production of IL-10 than subjects who were positive for the A allele. These results are in concordance with data presented in a study on stimulated purified blood lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

Sp1 binds to the G allele of the−1087 polymorphism in the IL-10 promoter and promotes IL-10 mRNA transcription and protein production

2010

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Interleukin (IL)-10 is an important cytokine in immune regulation and promotes B-cell proliferation and antibody production. High levels of IL-10 were found in subjects with autoimmune diseases. The A to G single nucleotide polymorphism at -1087 of the IL-10 promoter is associated with differences in promoter activity and IL-10 production. The objectives of this study were to analyze differences in the transcription factor binding to the -1087 IL-10 gene polymorphism in B-cells, the influence of the A to G transition on the IL-10 and Sp1 gene expression in B-cells after lipopolysaccharide (LPS) stimulation and the effect of knockdown of Sp1 on IL-10 gene expression. Using B-cell lines obtained from subjects with GG and AA genotypes for the À1087 polymorphism and chromatin immunoprecipitation assay, we showed that the transcription factors PU.1 and Spi-B bound to both G and A alleles, whereas the transcription factor Sp1 only bound to the G allele. LPS stimulation of the B-cells resulted in a larger increase in IL-10 and Sp1 gene expression for GG genotypes than AA genotypes and knockdown of Sp1 gene expression resulted in a decrease in IL-10 mRNA transcription. IL-10 production was higher for the GG genotype than for the AA genotype.

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“…177 Two small studies (no53) also failed to find a correlation between SNPs and TNF production. 178,179 Several larger studies have been conducted. A study by Huizinga et al 56 involving 179 subjects used a whole blood LPS stimulation assay, but found no statistical difference dependent on the 308 genotype.…”

Section: Ex Vivo Tnf Productionmentioning

confidence: 99%

Is there a future for TNF promoter polymorphisms?

2004

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The in vitro study of TNF promoter polymorphism (SNP) function was stimulated by the numerous case-control (association) studies of the polymorphisms in relation to human disease and the appearance of several studies claiming to show a functional role for these SNPs provided a further impetus to researchers interested in the role of TNF in their disease of interest. In this review we consider case-control studies, concentrating on the autoimmune and inflammatory diseases rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, and asthma, and on infectious diseases including malaria, hepatitis B and C infection, leprosy and sepsis/septic shock. We also review the available evidence on the functional role of the various TNF promoter polymorphisms. In general, case-control studies have produced mixed results, with little consensus in most cases on whether any TNF polymorphisms are actually associated with disease, although results have been more consistent in the case of infectious diseases, particularly malaria. Functional studies have also produced mixed results but recent work suggests that the much studied À308G/A polymorphism is not functional, while the function of other TNF polymorphisms remains controversial. Studies of the TNF region are increasingly using extended haplotypes that can better capture the variation of the MHC region.

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Association of Cytokine Polymorphic Inheritance and in Vitro Cytokine Production in Anti-Cd3/Cd28-Stimulated Peripheral Blood Lymphocytes1

Cited by 310 publications

References 39 publications

Differential interleukin-10 production stratified by −571 promoter polymorphism in purified human immune cells

Differential interleukin-10 production stratified by −571 promoter polymorphism in purified human immune cells

Sp1 binds to the G allele of the−1087 polymorphism in the IL-10 promoter and promotes IL-10 mRNA transcription and protein production

Is there a future for TNF promoter polymorphisms?

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