IL-6 is a differentiation factor for M1 and WEHI-3B myeloid leukemic cells.
IL-6 has multiple biologic activities in different cell systems including both the ability to support cell proliferation and to induce differentiation. We reported previously the isolation and functional expression of a mouse IL-6 (mIL-6) cDNA clone derived from bone marrow stromal cells. In this paper, we show that mIL-6 is a potent inducer of terminal macrophage differentiation for a mouse myeloid leukemic cell line, M1. Addition of mIL-6 to cultures of M1 cells rapidly inhibits their proliferation and induces phagocytic activity and morphologic changes characteristic of mature macrophages. These phenotypic changes are accompanied at the molecular level by a decrease in proto-oncogene c-myc mRNA accumulation and increases in Fc gamma R, proto-oncogenes c-fos and c-fms (CSF-1R) mRNA expression. Furthermore, IL-6 enhances the expression of Fc gamma R and c-fms in differentiation-responsive D+, but not unresponsive D- sublines of mouse myelomonocytic leukemic WEHI-3B cells. Together with our previous observation that IL-6 stimulates colony formation by normal myeloid progenitors, these results strongly suggest an important regulatory role for IL-6 in myeloid cell growth and differentiation.
Chiu
C P
CP
Department of Molecular Biology, DNAX Research Institute, Palo Alto, CA 94204-1104.
Lee
F
F
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006133:Growth Substances / Q000502:physiology*; D015850:Interleukin-6; D007378:Interleukins / Q000502:physiology*; D007700:Kinetics; D007951:Leukemia, Myeloid / Q000473:pathology*; D051379:Mice
D006133:Growth Substances; D015850:Interleukin-6; D007378:Interleukins