Regulation of monocyte and keratinocyte interleukin 6 production by transforming growth factor beta

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Abstract
There is strong evidence for a complex network‐like interaction between cytokines, growth factors and other mediators being responsible for cell growth and differentiation as well as for the outcome of an inflammatory reaction. Therefore, the regulation of the production of the ubiquitous proinflammatory cytokine interleukin 6 (IL‐6) by transforming growth factor β (TGFP) was investigated. Human peripheral blood mononuclear cells (PBMC), human normal keralinocytes (HNK), and an epidermoid carcinoma cell line (KB) were treated with TGFβ or TGFβ2 and subsequently IL‐6 secretion was evaluated. Addition of TGFβ1 as well as TGFβ2 to PBMC, HNK and KB cells resulted in a significantly increased release of IL‐6 activity. The inducing effect of TGFβ was dose dependent and maximal when supernatants were harvested 48 h after stimulation. In addition, upon Western blot analysis using a monoclonal IL‐6 antibody significantly increased amounts of IL‐6 protein were detected in KB cell supernatants following stimulation with TGFβ 1. These results were further confirmed at the transcriptional level using a cDNA probe specific for IL‐6 and Northern blot analysis. Accordingly, an increased IL‐6 inRNA expression in PBMC or KB cells was detected following TGFβl treatment. These findings indicate that TGFβ in contrast to its antiinflammatory capacities also may stimulate IL‐6 production in PBMC and keratinocytes. This further supports the possibly important immunoregulatory role of growth factors such as TGFβ.