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

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