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

Recent investigations have demonstrated that macrophage inhibitory protein 1alpha (MIP-1alpha) plays a critical role in haematopoiesis. In part, MIP-1alpha limits the differentiation of early haematopoietic cells, thereby ensuring that sufficient quantities of blood precursors are available to meet haematopoietic demands. MIP-1alpha is produced by cells of the marrow microenvironment (marrow stromal cells) in response to a variety of stimuli, including interleukin 1beta (IL-1beta) and tumour necrosis factor alpha (TNF-alpha). 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-1alpha remains one such possibility. In the present study, we investigated whether cells of the osteoblast lineage under basal, IL-1beta and/or TNF-alpha stimulation produce MIP-1alpha. We observed that IL-1beta and TNF-alpha stimulated HOBs and human osteosarcoma cells to rapidly express MIP-1alpha mRNA and to secrete large quantities of the protein. MIP-1alpha 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-1alpha mRNA by HOBs in vitro. These findings suggest that human osteoblast-like cells may produce MIP-1alpha in vivo to support haematopoiesis at sites where osteoblasts and haematopoietic cells are closely associated.