Regulation of systemic macrophage IL-i gene transcription: the involvement of tumor-derived macrophage growth factor

Previous data indicated that progressive growth of the C57BL/6J sarcoma, MCA/76-9, was associated with a systemic increase in the level of IL-i activity in peritoneal and tumor-associated macrophages. In this paper, the hypothesis was tested that macro-phage IL-i alpha and beta gene expression was regulated by the specific macrophage growth factor, CSF-i, produced by tumor cells. The data indicated that all of the nine C57BL/6J, BALB/CJ, and C3H/HeJ sarcomas tested transcribed the CSF-1 gene. The tu-mor cell culture supernates induced proliferation of bone marrow cells that differentiated into macrophages. Moreover, proliferative activity of conditioned medium and the ability to Induce macrophage differentiation were abrograted by neutralization with the 5Ai, rat-anti-mouse monoclonal anti-CSF-i antibody. Conditioned medium from tumor cell cultures, as well as recombinant CSF-i and L cell-conditioned medium, induced tran-scription of the IL-i alpha and beta genes, the latter being more strongly expressed. IL-i gene transcription was not induced after neutralization of the culture supernates by the monoclonal antibody, 5Ai. The overall data would support the hypothesis that the path-way in vivo leading to the increased IL-i expression by macrophages is regulated by at least one tumor cell product, CSF-i. Key words: mRNA, sarcomas, gene expressio