Production of Proinflammatory Cytokines and Cytokines Involved in the TH1/TH2 Balance Is Modulated by Pentoxifylline

Bienvenu, Jacques; Doche, Christophe; Gutowski, Marie-Claude; Lenoble, Michèle; Lepape, Alain; Perdrix, J.P.

doi:10.1097/00005344-199500252-00017

Cited by 86 publications

(47 citation statements)

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“…29 The 5 0 flanking region of the IL-10 gene, which regulates transcription, is polymorphic. 30 In particular, three such single-nucleotide polymorphisms (SNPs) have been identified and shown to influence IL-10 production levels.…”

Section: Introductionmentioning

confidence: 99%

Differential expression in lupus-associated IL-10 promoter single-nucleotide polymorphisms is mediated by poly(ADP-ribose) polymerase-1

et al. 2007

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Systemic lupus erythematosus (SLE) is a complex, multifactorial autoimmune disease characterized by the dysregulation of T and B cells that leads to hyperactivity of B cells and production of autoantibodies, and involves both environmental and genetic factors. Interleukin-10 (IL-10) is a candidate susceptibility gene in SLE. In particular, three IL-10 promoter singlenucleotide polymorphisms (SNPs; À1082A/G, À819T/C and À592A/C) are strongly associated with the pathogenesis of SLE. We found that the homozygous GCC haplotype linked to greater SLE severity confers higher IL-10 gene transcriptional activity than the ATA haplotype in macrophages that encounter apoptotic cells, because of the differential DNA binding to the À592 SNP by a nuclear protein uniquely induced by apoptotic cells. We identified this protein as poly(ADP-ribose) polymerase-1, confirmed its physiological role and characterized its molecular properties in modulating IL-10 production during phagocytosis of apoptotic cells. This study unveils a novel direct link between DNA damage repair/apoptosis pathways and IL-10-mediated immune regulation.

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Section: Introductionmentioning

confidence: 99%

Differential expression in lupus-associated IL-10 promoter single-nucleotide polymorphisms is mediated by poly(ADP-ribose) polymerase-1

et al. 2007

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“…9 IL-10 production is mostly regulated at the transcriptional level. 10 Several studies have suggested that the capacity to produce IL-10 is influenced by genetic factors. According to the results of a family study, there are striking inter-individual differences in IL-10 production following LPS stimulation.…”

Section: Introductionmentioning

confidence: 99%

Differential regulation of interleukin-10 production by genetic and environmental factors – a twin study

et al. 2002

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Interleukin-10 (IL-10) has a critical role in the regulation of immune responses. The relative contribution of genetic and environmental factors to IL-10 production is under debate. We performed a twin study in 246 monozygotic and dizygotic twins to assess the heritability of IL-10 production after LPS stimulation in whole blood. In addition, the influence of promoter single nucleotide polymorphisms (À1082, À819 and À592) on transcriptional activity and their binding to nuclear factors was studied in luciferase reporter gene and electrophoretic mobility shift assays. IL-10 production showed a genetic determination with a heritability of 0.5. Decreasing body mass index (BMI), smoking and female gender lead to decreased IL-10 production. In monocytes, the À1082A allele showed higher binding affinity to the transcription factor PU.1 resulting in decreased transcriptional activity of À1082A promoter haplotypes. Genetic determination of IL-10 secretion is probably lower than that previously reported. Fifty percent of the observed variability explained by genetic factors. Female individuals produce less IL-10 than male subjects. Environmental factors like smoking and decreasing BMI exert suppressing effects on IL-10 production. Although the À1082A allele shows higher binding affinity to the PU.1 transcription factor and lower transcriptional activity, this polymorphism probably explains only a small fraction of the observed heritability.

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“…On the other hand, it has been reported that PTX at high concentration suppressed Th2 cytokine production with a corresponding suppression of Th1 cytokines. 27 Rott et al demonstrated in a compact tissue that the systemic effects of a systemically administered drug were more robust than the regional effects, presumably because of differences in tissue distribution with oral PTX administration, 20 which would explain our finding of the different cytokine expression in the heart and the PBMC. Furthermore, it might be that the inhibitory mechanism of PTX in actively immunized EAM derives mainly from suppression of antigen-priming in the peripheral cells, not from regional defensive effects in the heart against the cellular infiltration.…”

Section: Immunomodulatory Mechanisms Of Ptx In Eammentioning

confidence: 78%

Immunomodulatory Effect of Pentoxifylline in Suppressing Experimental Autoimmune Myocarditis.

Takehana

Inomata

Niwano

et al. 2002

Circ J

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Production of Proinflammatory Cytokines and Cytokines Involved in the TH1/TH2 Balance Is Modulated by Pentoxifylline

Cited by 86 publications

References 0 publications

Differential expression in lupus-associated IL-10 promoter single-nucleotide polymorphisms is mediated by poly(ADP-ribose) polymerase-1

Differential expression in lupus-associated IL-10 promoter single-nucleotide polymorphisms is mediated by poly(ADP-ribose) polymerase-1

Differential regulation of interleukin-10 production by genetic and environmental factors – a twin study

Immunomodulatory Effect of Pentoxifylline in Suppressing Experimental Autoimmune Myocarditis.

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