| Autor: |
Heinsbroek SE; Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands., Squadrito ML; The Swiss Institute for Experimental Cancer Research (ISREC), École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., Schilderink R; Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands., Hilbers FW; Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands., Verseijden C; Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands., Hofmann M; Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands., Helmke A; Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands., Boon L; EPIRUS Biopharmaceuticals Netherlands BV, Utrecht, The Netherlands., Wildenberg ME; Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands., Roelofs JJ; Department of Pathology, Academic Medical Center, University of Amsterdam, AMC, Amsterdam, The Netherlands., Ponsioen CY; Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands., Peters CP; Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands., Te Velde AA; Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands., Gordon S; Sir William Dunn School of Pathology, University of Oxford, Oxford, UK., De Palma M; The Swiss Institute for Experimental Cancer Research (ISREC), École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland., de Jonge WJ; Academic Medical Center, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AMC, Amsterdam, The Netherlands. |
| Abstrakt: |
MiR-511-3p is embedded in intron 5 of the CD206/MRC1 gene Mrc1, expressed by macrophage and dendritic cell populations. CD206 and miR-511-3p expression are co-regulated, and their contribution to intestinal inflammation is unclear. We investigated their roles in intestinal inflammation in both mouse and human systems. Colons of CD206-deficient mice displayed normal numbers of monocytes, macrophage, and dendritic cells. In experimental colitis, CD206-deficient mice had attenuated inflammation compared with wild-type (WT) mice. However, neither a CD206 antagonist nor a blocking antibody reproduced this phenotype, suggesting that CD206 was not involved in this response. Macrophages isolated from CD206-deficient mice had reduced levels of miR-511-3p and Tlr4 compared with WT, which was associated with reduced pro-inflammatory cytokine production upon lipopolysaccharides (LPS) and fecal supernatant stimulation. Macrophages overexpressing miR-511-3p showed 50% increase of Tlr4 mRNA, whereas knockdown of miR-511-3p reduced Tlr4 mRNA levels by 60%, compared with scrambled microRNA (miRNA)-transduced cells. Response to anti-tumor necrosis factor (TNF) treatment has been associated with elevated macrophage CD206 expression in the mucosa. However, in colon biopsies no statistically significant change in miR-511-3p was detected. Taken together, our data show that miR-511-3p controls macrophage-mediated microbial responses and is involved in the regulation of intestinal inflammation. |
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