title: Interleukin-6 enhances transforming growth factor-alpha mRNA expression in macrophage-like human monocytoid (U-937-1) cells.
abstract: We have previously reported that the human monocytoid cell line U-937-1 constitutively expresses transforming growth factor-alpha (TGF-alpha) and that the steady-state levels of TGF-alpha mRNA as well as TGF-alpha protein release increase when U-937-1 cells are differentiated towards monocytes/macrophages. Interleukin-6 (IL-6), which has been shown to have growth-stimulatory effects on a number of cell types, has recently been shown to enhance TGF-alpha expression in keratinocytes. In the present study we investigated whether TGF-alpha expression in macrophage-like cells could be regulated by IL-6 using U-937-1 cells as a model system of monocyte/macrophage differentiation. U-937-1 cells were differentiated with retinoic acid (RA), vitamin D3 (Vit-D3) or phorbol-12-myristate-13-acetate (PMA) for 4 days and were then treated with human recombinant IL-6 (1000 IU/ml) for up to 24 hr. Northern blot analysis revealed that cells differentiated with PMA, inducing the phenotype of a secretory macrophage, markedly increased their TGF-alpha mRNA levels (2.7-fold) when treated with IL-6; the response was maximal at 6 hr and remained high at 12 hr. The expression of the TGF-alpha gene was accompanied by release of TGF-alpha protein into the cell culture medium, irrespective of differentiating agent, as demonstrated by enzyme-linked immunosorbent assay (ELISA), as well as by surface expression of pro-TGF-alpha as determined by indirect immunofluorescent cytometry. However, the superinduction of the TGF-alpha gene by IL-6 in cells differentiated with PMA was not accompanied by any increase in TGF-alpha protein release or pro-TGF-alpha surface expression. We conclude that since IL-6 causes increased steady-state levels of TGF-alpha mRNA in macrophage-like cells, it may prime these cells for production of this growth factor. Furthermore, we have shown that the IL-6 receptor complex is functional in U-937-1 cells induced to differentiate towards a secretory macrophage by treatment with PMA.
authors.affiliation: Department of Biomedicine and Surgery, Division of Cell Biology, University of Linkoping, Sweden. annha@mcb.liu.se
authors.forename: A L
authors.initials: AL
authors.lastname: Hallbeck
authors.forename: T M
authors.initials: TM
authors.lastname: Walz
authors.forename: A
authors.initials: A
authors.lastname: Wasteson
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002762:Cholecalciferol / Q000494:pharmacology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000187:drug effects* / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000235:genetics* / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
chemical_list: D015850:Interleukin-6; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D016211:Transforming Growth Factor alpha; D002762:Cholecalciferol; D014212:Tretinoin; D013755:Tetradecanoylphorbol Acetate