Methylation of the CpG at -299 bp from transcription start site of interleukin-1β is a sustained marker of inflammation exerted by TNFa on bone marrow-derived mesenchymal cells of healthy humans

Abstract

Background The role of bone marrow mesenchymal cells is demonstrated both in normal conditions and in various pathologies of the hematopoietic system. The regulatory functions of mesenchymal cells are so significant that they themselves and their secretome or extracellular vesicles are used for the treatment and prevention of immune complications during transplantation and in other aspects of regenerative medicine. As shown earlier, interleukin-1β (IL1B) is an important factor regulating the activity of the bone marrow stroma. Methods Methylation profile of IL1B promoter and IL1B expression were measured in cultured mesenchymal cells obtained from the bone marrow of healthy donors. IL1B expression was also measured upon different inflammatory stimuli including tumor necrosis factor-α (TNF). Results For healthy donor mesenchymal cells, we observed differences in IL1Bpromoter methylation profile at the position of one CpG at -299 bp from transcription start site, which is a part of or in immediate proximity to binding sites of NF-kB transcription factors. The study establishes a link among TNF exposure, the CpG methylation, and IL1B expression during and after exposure. Conclusion Since TNF is a pro-inflammatory factor that is associated with damage and aging, it is concluded that for healthy donor mesenchymal cells, the observed differences in IL1B promoter methylation profile may be a long-term imprint of inflammatory processes previously sustained by a person, as well as a marker of physiological differences in the human bone marrow stroma.