Tumor cell IL-6 gene expression is regulated by IL-1 alpha/beta and TNF alpha: proposed feedback mechanisms induced by the interaction of tumor cells and macrophages.
Cell-Division: ph, Feedback, Gene-Expression-Regulation-Neoplastic: ge, ph, Interleukin-1: ph, me, Interleukin-6: bl, ge, se, Macrophage-Activation: ph, Macrophages: ph, Male, Mice, Mice-Inbred-BALB-C, Neoplasm-Transplantation, Receptors-Interleukin-1: ph, me, Rhabdomyosarcoma: ge, me, pa, SUPPORT-U-S-GOVT-P-H-S, Transcription-Genetic: de, Translation-Genetic: de, ph, Tumor-Cells-Cultured, Tumor-Necrosis-Factor: ph
J Leukoc Biol 1992 Oct;52(4):463-8
In the present report, we show that progressive growth of the immunogenic C57BL/6J sarcoma, MCA/76-9, was accompanied by an increase in serum interleukin-6 (IL-6) activity. The possible pathways leading to the induction of IL-6 release by the tumor cells are described. It was shown that macrophage products IL-1 alpha, IL-1 beta, and to a lesser extent, TNF alpha, induced the tumor cells in vitro to transcribe the IL-6 gene and release the gene product. IL-1 induced significantly more IL-6 mRNA and bioactivity than TNF alpha, although both cytokines induced a cumulative increase of bioactivity in the supernates over a period of 24 h. The tumor cells were shown to express receptors for IL-1 alpha, which could be blocked with anti-IL-1 receptor antibody. Given the previous reports that tumor-associated macrophages expressed both IL-1 alpha/beta and TNF alpha, the data suggest, first, that the mutual interaction of tumor cells and macrophages in situ may contribute to the observed increase in circulating IL-6 activity, and second, that the release of IL-6 in vivo may serve to regulate both anti-tumor immune responses and suppressor mechanisms.
Evans, R; Fong, M; Fuller, J; Kamdar, S; Meyerhardt, J; and Strassmann, G, " Tumor cell IL-6 gene expression is regulated by IL-1 alpha/beta and TNF alpha: proposed feedback mechanisms induced by the interaction of tumor cells and macrophages." (1992). Faculty Research 1990 - 1999. 284.