Differentiation and activation associated expression of IL-6 and IL-6 receptors in U-937 monocytic cells: relationship to the expression of CD14.
Activated monocytes play an important role as producers of IL-6 during inflammation and immune response. We show that during monocytic differentiation of U-937 cells, induced by phorbolester (PMA), IL-6 mRNA expression was transiently up-regulated and IL-6 protein was secreted into the medium. In contrast, differentiation induced by VitD3 or Retinoic acid (RA) did not lead to an increase in the IL-6 expression. Thus, IL-6 expression does not seem to be associated with monocyte differentiation per se. However, U-937 cells terminally differentiated by VitD3, rapidly responded to bacterial lipopolysaccharide (LPS) induced activation by IL-6 expression and secretion. In cells, differentiated by PMA, the IL-6 expression was super-induced after activation by interferon-gamma (IFN-gamma) and LPS. The capacity of U-937 cells to respond to LPS activation by IL-6 expression was associated with the expression of CD14 and some serum components(s) were a prerequisite for a successful LPS induction. The IL-6R expression was down-regulated during monocytic differentiation of U-937 cells. In the terminally differentiated U-937 cells, the expression of IL-6R could be induced after activation by IFN-gamma and to a lesser extent by LPS, suggesting a mechanism by which activation positively regulates the response to IL-6 in macrophages.
Oberg
F
F
Department of Pathology, Uppsala University, University Hospital, Sweden.
Nilsson
K
K
D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis* / Q000235:genetics; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D015870:Gene Expression / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides / Q000633:toxicity; D016403:Lymphoma, Large B-Cell, Diffuse; D009000:Monocytes; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D011971:Receptors, Immunologic; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014212:Tretinoin; D007371:Interferon-gamma; D002117:Calcitriol; D013755:Tetradecanoylphorbol Acetate