Data_Sheet_1_Human Red Blood Cells Modulate Cytokine Expression in Monocytes/Macrophages Under Anoxic Conditions.pdf

In the bone marrow (BM) hematopoietic niche, the oxygen tension is usually very low. Such condition affects stem and progenitor cell proliferation and differentiation and, at cellular level regulates hematopoietic growth factors, chemokines and adhesion molecules expression. In turn, these molecules affect the proliferation and maturation of other cellular components of the niche. Due to the complexity of the system we started the in vitro investigations of the IL-6, IL-8, TNFα cytokines expression and the vascular endothelial growth factor (VEGF), considered key mediators of the hematopoietic niche, in human macrophages and macrophage cell line. Since in the niche the oxygen availability is mediated by red blood cells (RBCs), we have influenced the anoxic cell cultures by the administration of oxygenated or deoxygenated RBCs (deoxy RBCs). The results reported in this brief paper show that the presence of RBCs up-regulates IL-8 mRNA while IL-6 and VEGF mRNA expression appears down-regulated. This does not occur when deoxy RBCs are used. Moreover, it appears that the administration of RBCs leads to an increase of TNFα expression levels in MonoMac 6 (MM6). Interestingly, the modulation of these factors likely occurs in a hypoxia-inducible factor-1α (HIF-1α) independent manner. Considering the role of oxygen in the hematopoietic niche further studies should explore these preliminary observations in more details.

在骨髓（bone marrow, BM）造血微环境中，氧张力通常极低。此种状态会影响造血干祖细胞的增殖与分化，并在细胞层面调控造血生长因子、趋化因子及黏附分子的表达。反过来，这些分子又会影响微环境中其他细胞组分的增殖与成熟。鉴于该系统的复杂性，我们开展了体外研究，针对人巨噬细胞及巨噬细胞系中IL-6、IL-8、TNFα细胞因子与血管内皮生长因子（vascular endothelial growth factor, VEGF）的表达进行分析——上述因子被认为是造血微环境的关键介导分子。由于微环境中的氧可用性由红细胞（red blood cells, RBCs）介导，我们通过输注氧合红细胞或脱氧红细胞（deoxygenated RBCs, deoxy RBCs）来调控缺氧细胞培养环境。本短篇论文报道的结果显示：红细胞的存在会上调IL-8的mRNA表达，而IL-6与VEGF的mRNA表达则呈现下调趋势；使用脱氧红细胞时则不会出现上述变化。此外，红细胞的输注会使MonoMac 6（MM6）细胞中的TNFα表达水平升高。值得注意的是，这些因子的调控似乎不依赖于缺氧诱导因子-1α（hypoxia-inducible factor-1α, HIF-1α）。考虑到氧在造血微环境中的作用，后续研究应进一步深入探索这些初步发现。