Human osteoblast-like cells and osteosarcoma cell lines synthesize macrophage inhibitory protein 1α in response to interleukin 1β and tumour necrosis factor α stimulation in vitro

Recent investigations have demonstrated that macrophage inhibitory protein 1α (MIP-1α) plays a critical role in haematopoiesis. In part, MIP-1α limits the differentiation of early haematopoietic cells, thereby ensuring that sufficient quantities of blood precursors are available to meet haematopoietic demands. MIP-1α is produced by cells of the marrow microenvironment (marrow stromal cells) in response to a variety of stimuli, including interleukin 1β (IL-1β) and tumour necrosis factor α (TNF-α). Our recent investigations demonstrated that normal human osteoblast-like cells (HOBs) maintain the early phenotype of haematopoietic precursors, like other members of the bone marrow stroma. Although the precise molecular mechanisms for these observations have not been determined, the production of MIP-1α remains one such possibility. In the present study, we investigated whether cells of the osteoblast lineage under basal, IL-1β and/or TNF-α stimulation produce MIP-1α. We observed that IL-1β and TNF-α stimulated HOBs and human osteosarcoma cells to rapidly express MIP-1α mRNA and to secrete large quantities of the protein. MIP-1α mRNA and protein was not, however, detected under basal conditions. Perhaps more importantly, enriched human CD34⁺ bone marrow cells in co-culture may be capable of stimulating the expression of MIP-1α mRNA by HOBs in vitro. These findings suggest that human osteoblast-like cells may produce MIP-1αin vivo to support haematopoiesis at sites where osteoblasts and haematopoietic cells are closely associated.