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Interleukin (IL)-22 is a STAT3-activating cytokine displaying characteristic AU-rich elements (ARE) in the 3'-untranslated region (3'-UTR) of its mRNA. This architecture suggests gene regulation by modulation of mRNA stability. Since related cytokines undergo post-transcriptional regulation by ARE-binding tristetraprolin (TTP), the role of this destabilizing protein in IL-22 production was investigated. Herein, we demonstrate that TTP-deficient mice display augmented serum IL-22. Likewise, IL-22 mRNA was enhanced in TTP-deficient splenocytes and isolated primary T cells. A pivotal role for TTP is underscored by an extended IL-22 mRNA half-life detectable in TTP-deficient T cells. Luciferase-reporter assays performed in human Jurkat T cells proved the destabilizing potential of the human IL-22-3'-UTR. Furthermore, overexpression of TTP in HEK293 cells substantially decreased luciferase activity directed by the IL-22-3'-UTR. Transcript destabilization by TTP was nullified upon cellular activation by TPA/A23187, an effect dependent on MEK1/2 activity. Accordingly, IL-22 mRNA half-life as determined in TPA/A23187-stimulated Jurkat T cells decreased under the influence of the MEK1/2 inhibitor U0126. Altogether, data indicate that TTP directly controls IL-22 production, a process counteracted by MEK1/2. The TTP-dependent regulatory pathway described herein likely contributes to the role of IL-22 in inflammation and cancer and may evolve as novel target for pharmacological IL-22 modulation.
NLP4CMC III : 3rd workshop on natural language processing for computer-mediated communication
(2016)
The present paper reports the first results of the compilation and annotation of a blog corpus for German. The main aim of the project is the representation of the blog discourse structure and relations between its elements (blog posts, comments) and participants (bloggers, commentators). The data included in the corpus were manually collected from the scientific blog portal SciLogs. The feature catalogue for the corpus annotation includes three types of information which is directly or indirectly provided in the blog or can be construed by means of statistical analysis or computational tools. At this point, only directly available information (e.g., title of the blog post, name of the blogger etc.) has been annotated. We believe, our blog corpus can be of interest for the general study of blog structure or related research questions as well as for the development of NLP methods and techniques (e.g. for authorship detection).