Taken together with the observation that IL-10 production by monocytes, in the early in vitro response to TG, is under T-cell control, these findings suggest that the prior, in vivo, encounter with TG may have served to establish active tolerance against this autoantigen. Clearly, it is of interest BMS-777607 order to define more precisely the T-cell subpopulation responsible for this regulatory activity and to establish whether the regulatory response, described here for TG, applies for autoantigens in general.

Our recent findings that the autoantigen, myelin basic protein, also induces a marked IL-10 response by normal PBMC within one day of incubation, while the corresponding response of untreated multiple sclerosis patients is diminished, suggest that this might be the case.29 The authors wish to thank Nanna Bøgesvang and Winnie Hansen for their expert technical assistance. This study was supported by The Novo Nordisk Foundation, the A. P.

Møller and Chastine Mc-Kinney Møller’s Foundation, Erik Hørslev and spouse Birgit Hørslev’s Selleck JQ1 Foundation, King Christian the Tenth’s Foundation, Carla Thiel Kragh’s Foundation, Oda and Hans Svenningensen’s Foundation and Director Jacob Madsen and spouse Olga Madsen’s Foundation. None of the authors have financial conflicts of interest in relation to this work. “
“Citation Sharma S, Stabila J, Pietras L, Singh AR, McGonnigal B, Ernerudh J, Matthiesen L, Padbury JF. Haplotype-dependent differential activation of the human IL-10 gene promoter in macrophages and trophoblasts: Implications for placental IL-10 deficiency and pregnancy complications. Am J Reprod Immunol 2010; 64: 179–187 Problem  Polymorphic changes in the IL-10 gene promoter have been identified that lead to altered IL-10 production. We hypothesized that because of these genotypic changes, the IL-10 promoter might be expressed in a cell heptaminol type–specific manner and may respond differentially to inflammatory triggers. Method of study  We created reporter gene promoter constructs containing

GCC, ACC, and ATA haplotypes using DNA from patients harboring polymorphic changes at −1082 (GA), −819 (CT), and −592 (CA) sites in the IL-10 promoter. These individual luciferase reporter constructs were transiently transfected into either primary term trophoblasts or THP1 monocytic cells. DNA-binding studies were performed to implicate the role of the Sp1 transcription factor in response to differential promoter activity. Results  Our results suggest that the GCC promoter construct was activated in trophoblast cells in response to lipopolysaccharide (LPS), as demonstrated by reporter gene expression, but not in monocytic cells. The ACC construct showed weaker activation in both cell types.