ABSTRACT
Interleukin-1 beta (IL1B) is a key inducer of inflammation and an important factor in the regulation of hematopoietic stem cells and mesenchymal stromal progenitors. Irradiation of mice with ionizing radiation has been shown to induce a lasting increase in IL1B concentration in peripheral blood. One of the possible mechanisms may be demethylation of CpG cytosines in the Il1b promoter, which has not been characterized in detail for the mouse. In this study, the methylation level of CpGs located in a region between -3562 and -208 bp upstream of the start of transcription is studied in muscles, bones, liver, thymus, spleen, bone marrow, lymph nodes, lungs, and brain. The methylation level is compared to Il1b expression. Tissue-specific features of CpG methylation are established. It is demonstrated that the region between -2420 and -2406 bp is likely a part of the mouse Il1b promoter/enhancer and may determine the base level of Il1b expression in various tissues. Irradiation at a dose of 6 Gy does not change the methylation profile of most studied CpGs, and therefore, the cause of the stably increased IL1B level after irradiation is unlikely to be a change in the methylation of the studied CpGs in investigated tissues.
Subject(s)
Gamma Rays , Interleukin-1beta/genetics , Promoter Regions, Genetic/genetics , Animals , Bone and Bones/metabolism , Bone and Bones/radiation effects , CpG Islands/genetics , DNA Methylation/radiation effects , Female , Gene Expression Regulation/radiation effects , Humans , Mice , Promoter Regions, Genetic/radiation effects , Transcription Factors/metabolismABSTRACT
The efficacy and the safety of the administration of multipotent mesenchymal stromal cells (MMSCs) for acute graft-versus-host disease (aGVHD) prophylaxis following allogeneic hematopoietic cell transplantation (HSCT) were studied. This prospective clinical trial was based on the random patient allocation to the following two groups receiving (1) standard GVHD prophylaxis and (2) standard GVHD prophylaxis combined with MMSCs infusion. Bone marrow MMSCs from hematopoietic stem cell donors were cultured and administered to the recipients at doses of 0.9-1.3 × 10(6)/kg when the blood counts indicated recovery. aGVHD of stage II-IV developed in 38.9% and 5.3% of patients in group 1 and group 2, respectively, (P = 0.002). There were no differences in the graft rejection rates, chronic GVHD development, or infectious complications. Overall mortality was 16.7% for patients in group 1 and 5.3% for patients in group 2. The efficacy and the safety of MMSC administration for aGVHD prophylaxis were demonstrated in this study.
