Biomedical subjects

S Bulfone-Paus

Publications and source records attributed to S Bulfone-Paus.

41 records · Page 3Linked to original sources

PubMed1996

Genomic structure and chromosomal localization of the human interleukin 15 gene (IL-15).

Interleukin 15 (IL-15) is a novel cytokine whose biological activities are similar to those of interleukin 2 (IL-2). The genomic sequence of human IL-15 has been isolated based on its sequence homology with a cDNA clone encoding human IL-15. The human sequence is 14968 bp in length and includes all six protein-coding exons and five introns. The location of the introns in the human sequence is identical to their positions in the murine IL-15 gene. The same is true for the overall size of the gene, which was estimated to be at least 32 kb. Using Polymerase Chain Reaction (PCR) with gene-specific primers on a panel of human/rodent hybrid cell DNAs, as well as by fluorescence in situ hybridization the human IL-15 gene was mapped to chromosome 4 region q25-35.

Amino Acid Sequence↗

PubMed1996

Immunomodulation in experimental and clinical nephrology using chimeric proteins.

The objective of immunosuppressive therapy in nephrology is to prevent autoimmune diseases and to suppress kidney allograft rejections while sparing other effects. Increased clarification of the underlying immune mechanism has made specific immunodulation possible using chimeric proteins in which the variable domains of an immunoglobulin are replaced by extracellular domains of cell surface molecules or cytokines. The immunosuppressive effects of fusion proteins such as CTLA-4 IgG, CD40 IgG, interleukin (IL)-10 IgG, IL-2 IgG or tumor necrosis factor (TNF)-receptor IgG have been proven in various animal models. Moreover, the application of TNF-receptor IgG successfully limited the OKT3-induced cytokine release syndrome in kidney graft recipients. It seems likely that recombinant proteins with increasingly effective suppression of specific elements of the immune response will become an essential element in clinical protocols.

Abatacept↗

PubMed1995

Host factors LR1 and Sp1 regulate the Fp promoter of Epstein-Barr virus.

The Epstein-Barr virus EBNA-1 gene product is essential for latent replication of the virus. In transformed cells characterized by the most restricted patterns of viral latent gene expression, EBNA-1 transcription is driven from the Fp promoter. We have used genetic and biochemical techniques to study the promoter-proximal elements that regulate Fp expression in B cells. We show that a 114-bp fragment of DNA spanning the Fp "TATA" box functions as a remarkably active transcriptional regulatory element in B cells. Two host factors, Sp1 and LR1, regulate Fp transcription from the promoter-proximal region. Sp1 binds a single site just downstream of the TATA box, and LR1 binds two sites just upstream of the TATA box. Transcripts from both the viral genome and the minimal promoter initiate at the same unique site, and one function of LR1 at Fp is to direct initiation to this unique start site. In contrast to Sp1, which is ubiquitous, LR1 is present only in activated B cells and may contribute to cell-type-specific transformation by Epstein-Barr virus.

Antigens, Viral↗

PubMed1995

The chicken immunoglobulin lambda light chain gene is transcriptionally controlled by a modularly organized enhancer and an octamer-dependent silencer.

Characterization of the regulatory elements involved in V(D)J recombination is crucial for understanding development of the B and T cell immune repertoire. Previously we have shown that the chicken immunoglobulin lambda light chain gene (CLLCG) undergoes lymphoid-specific rearrangement in transgenic mice. The whole gene is only 10 kb in length and contains all phylogenetically conserved target sites for recombinational and transcriptional regulation. In this study we have localized an enhancer element in a region 4 kb downstream of the constant (C) region. The 467 bp element can be subdivided into three subfragments. The previously detected silencer element on the V-J intervening sequence is shown to be localized on a 500 bp fragment. Partial silencer activity is retained on a 250 bp fragment, which includes an octamer motif. By mutational analysis this octamer is shown to be essential for B cell- but not for T cell-specific silencer function. The silencer represses transcription directed by heterologous elements like the SV 40 promoter or the Ig kappa 3' enhancer. We propose that transcription of the unrearranged and rearranged Ig genes is regulated by complex interactions between different modules from the promoter, enhancer and silencer, which is eliminated by recombination during B cell development.

Animals↗

PubMedDate not supplied

Reduced cumulative incidence of diabetes but not insulitis following administration of chimeric human IL-15-murine IgG2b in NOD mice.

BACKGROUND: It has been recently demonstrated that apoptosis is involved in beta-cell destruction in the NOD mouse model of diabetes. The aim of the present study was to investigate whether IL-15, a cytokine involved in the modulation of the apoptotic process, is capable of modifying the natural history of diabetes and/or insulitis in pre-diabetic NOD mice. The rationale for the use of IL-15-IgG2b recombinant cytokine is related to its long half-life (28 +/- 4 h). METHODS: At 10 weeks of age, 2 groups of 24 female mice were treated with single or multiple i.p. doses of IL-15-IgG2b respectively. As control, 2 groups of 24 age- and litter-matched female mice were injected intra-peritoneally with single or multiple doses of IgG2b immunoglobulin. RESULTS: Diabetes incidence at 33 weeks of age was lower in the group of mice treated with multiple doses than in the control group (p = 0.03). The cumulative incidence of diabetes at 33 weeks of age between single-dose treated mice and the control group was similar. No significant differences in the calculated index of insulitis were observed in all treated and control mice. CONCLUSIONS: We conclude that IL-15-IgG2b reduces the cumulative incidence of diabetes, without affecting the extent and severity of the insulitis process. Considering this and the well-defined anti-apoptotic effects of IL-15, we suggest that the reduction of diabetes incidence could be due to a down-regulation of beta-cell apoptosis.

Animals↗