Regulation of the expression of IL-6 in human monocytes

• Published in: The Journal of immunology (1950) Vol. 142; no. 12; pp. 4339 - 4345
• Main Authors: Navarro, S, Debili, N, Bernaudin, JF, Vainchenker, W, Doly, J
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.06.1989
• Subjects: Cell Adhesion; Cell Differentiation - drug effects; Cell Line; Gene Expression Regulation - drug effects; Humans; Interleukin-6; Interleukins - biosynthesis; Interleukins - genetics; Interleukins - pharmacology; Leukocytes, Mononuclear - metabolism; Monocytes - metabolism; Monocytes - physiology; Recombinant Proteins - pharmacology; Tetradecanoylphorbol Acetate - pharmacology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.142.12.4339

IL-6 is a cellular regulatory molecule with various cell-dependent functions. We have studied the control of IL-6 expression in human monocytes because they play a key role in the production of this molecule. The effects of adherence and different cytokines including CSF-1, IFN-gamma, IL-1 alpha, and granulocyte-macrophage-CSF were tested on IL-6 expression. IL-6 mRNA was usually not detected in the starting population of PBMC. Adherence induced IL-6 gene expression in monocytes in less than 2 h and subsequently IL-6 secretion. Priming of monocytes by adherence was more efficient for IL-6 overinduction by CSF-1. In contrast, high level induction of IL-6 by IFN-gamma in unfractionated PBMC did not require adherence and in situ hybridization revealed that IL-6 mRNA was present in monocytes but not in lymphocytes. A similar phenomenon was observed for IL-1 alpha and granulocyte-macrophage-CSF. Two cell lines, HL-60 and U937, in which monocytic differentiation occurs after induction by PMA, were subsequently investigated. IL-6 was not constitutively detectable in these two cell lines, whereas PMA treatment induced IL-6 expression. This effect was rapid (30 min) and transitory in HL-60, whereas IL-6 mRNA was still detected after 72 h of induction in U937. Addition of human rIL-6 on U937 and HL-60 cells inhibited their proliferation and enhanced expression of HLA class I Ag.