Recruitment of CCR6-expressing Th17 cells by CCL20 secreted from plasmin-stimulated macrophages Qun Li, Yves Laumonnier, Tatiana Syrovetsand Thomas Simmet Joint Laboratory of Vascular Biology of Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China Acta Biochim Biophys Sin 2013, 45: 593–600; doi: 10.1093/abbs/gmt049 In the present study, monocyte-derived human macrophages were differentiated from buffy coats. Nave CD4+ T-cells enriched from peripheral blood mononuclear cells using anti-CD4 magnetic beads and the autoMACS separation system were polarized under T-helper 17 (Th17)-promoting conditions for 6 days to get Th17 cells. The frequency of Th17 cell differentiation and the expression of C-C chemokine receptor type 6 (CCR6) on Th17 cells were investigated by flow cytometry. Plasmin-triggered induction of macrophage inflammatory protein-3alpha/C-C chemokine ligand 20 (CCL20) genes in macrophages was assessed by reverse transcription-polymerase chain reaction, and secreted protein levels were measured by enzyme-linked immunosorbent assay. Th17 cell migration induced by CCL20 secreted from plasmin-stimulated macrophages was tested in vitro by chemotaxis using a transwell system. These results demonstrate that plasmin triggers the expression of chemokine CCL20 messenger RNA and the release of CCL20 protein in human monocyte-derived macrophages, which critically depend on the proteolytic activity of plasmin and activation of p38 mitogen-activated protein kinase and nuclear factor-kappaB signaling pathways. Expression of CCR6 was detected on 87.23 ± 8.6% of Th17 cells in vitro. Similar to chemotaxis triggered by recombinant human CCL20, supernatants collected from plasmin-stimulated macrophage-induced chemotactic migration of Th17 cells, which could be inhibited by an anti-CCL20 neutralizing antibody. These results suggest that plasmin generated in inflamed tissues might elicit production of chemokine CCL20 by human macrophages leading to the recruitment of CCR6 positive Th17 cells to the inflammatory sites. CCL20 induces the Th17 cell migration 全文: http://abbs.oxfordjournals.org/content/45/7/593.full.pdf+html 相关论文: 1 The chemokine receptor CCR6 facilitates the onset of mammary neoplasia in the MMTV-PyMT mouse model via recruitment of tumor-promoting macrophages 2 CCL20 mediates lipopolysaccharide induced liver injury and is a potential driver of inflammation and fibrosis in alcoholic hepatitis 3 Identification of CD300a as a new hypoxia-inducible gene and a regulator of CCL20 and VEGF production by human monocytes and macrophages 4 CCL20 /CCR6 promotes the invasion and migration of thyroid cancer cells via NF-kappa B signaling-induced MMP-3 production 5 CCR6, the Sole Receptor for the Chemokine CCL20 , Promotes Spontaneous Intestinal Tumorigenesis 6 CCR6 and CCL20 : emerging players in the pathogenesis of rheumatoid arthritis
标签: CCR5
