IL6 May Have Autocrine Functions
In this study, the reasearchers performed siRNA-mediated gene silencing and RNA sequencing in order to study the autocrine functions of IL6 in cultured human endothelial cells. In contrast to the general assumption that the IL6Rα is only expressed on leucocytes and hepatocytes , they recently showed that human endothelial cells do express functional IL6Rα on their surface, and that exposure to IL6 causes intracellular signaling in human endothelial cells. Then further reported that IL6 classic signaling and transsignaling in human endothelial cells induce distinct molecular signaling events resulting in different cellular responses. In the current study, knockdown of IL6 was performed in the presence and absence of sIL6Rα in order to study the autocrine functions of IL6 in human endothelial cells under conditions which allow for both classic signaling and transsignaling..
Data obtained in the present study confirm that IL6 acts in an autocrine manner in human endothelial cells, as knockdown of IL6 results in alteration in gene expression of a large number of genes. Furthermore, exposure of endothelial cells to the sIL6Rα induces an increase in the release of IL6, suggesting that the activation of IL6 transsignaling induces a positive feedback loop, resulting in further synthesis and release of IL6. This concept has been proposed for IL6-mediated transsignaling but has so far not been shown for IL6-mediated classic signaling. They also report here that the mRNA expression of IL6Rα as well as the signal-transducer gp130 are upregulated after IL6 knockdown. This is in line with what they previously showed on protein level and suggests that the cells compensate the loss of signal from IL6 by increasing the expression of the receptors.
This study shows that knockdown of IL6 in human endothelial cells results in dramatic changes in transcriptional pattern, and a large number of novel genes that are under autocrine regulation by IL6 in human endothelial cells were identified. The present study also reveals that the autocrine functions of IL6 in human endothelial cells seem to be related to basal cellular functions such as regulation of cell cycle, signaling, or cellular movement, and suggests that the autocrine functions of IL6 in human endothelial cells are mediated via IL6 classic signaling.
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