2. Academic Validation
  3. C-C Motif Ligand 20 (CCL20) and C-C Motif Chemokine Receptor 6 (CCR6) in Human Peripheral Blood Mononuclear Cells: Dysregulated in Ulcerative Colitis and a Potential Role for CCL20 in IL-1β Release

C-C Motif Ligand 20 (CCL20) and C-C Motif Chemokine Receptor 6 (CCR6) in Human Peripheral Blood Mononuclear Cells: Dysregulated in Ulcerative Colitis and a Potential Role for CCL20 in IL-1β Release

  • Int J Mol Sci. 2018 Oct 20;19(10):3257. doi: 10.3390/ijms19103257.
Helene Kolstad Skovdahl 1 2,  Jan Kristian Damås 3 4 5,  Atle van Beelen Granlund 6 7,  Ann Elisabet Østvik 8 9 10,  Berit Doseth 11 12 13,  Torunn Bruland 14 15,  Tom Eirik Mollnes 16 17 18 19,  Arne Kristian Sandvik 20 21 22
Affiliations

Affiliations

  • 1 Centre of Molecular Inflammation Research, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway. helene.k.skovdahl@ntnu.no.
  • 2 Department of Clinical and Molecular Medicine, NTNU, 7030 Trondheim, Norway. helene.k.skovdahl@ntnu.no.
  • 3 Centre of Molecular Inflammation Research, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway. jan.k.damas@ntnu.no.
  • 4 Department of Clinical and Molecular Medicine, NTNU, 7030 Trondheim, Norway. jan.k.damas@ntnu.no.
  • 5 Department of Infectious Diseases, St. Olav's University Hospital, 7030 Trondheim, Norway. jan.k.damas@ntnu.no.
  • 6 Centre of Molecular Inflammation Research, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway. atle.granlund@ntnu.no.
  • 7 Department of Clinical and Molecular Medicine, NTNU, 7030 Trondheim, Norway. atle.granlund@ntnu.no.
  • 8 Centre of Molecular Inflammation Research, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway. ann.e.ostvik@ntnu.no.
  • 9 Department of Clinical and Molecular Medicine, NTNU, 7030 Trondheim, Norway. ann.e.ostvik@ntnu.no.
  • 10 Department of Gastroenterology and Hepatology, St. Olav's University Hospital, 7030 Trondheim, Norway. ann.e.ostvik@ntnu.no.
  • 11 Centre of Molecular Inflammation Research, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway. berit.doseth@ntnu.no.
  • 12 Department of Clinical and Molecular Medicine, NTNU, 7030 Trondheim, Norway. berit.doseth@ntnu.no.
  • 13 Clinic of Medicine, St. Olav's University Hospital, 7030 Trondheim, Norway. berit.doseth@ntnu.no.
  • 14 Department of Clinical and Molecular Medicine, NTNU, 7030 Trondheim, Norway. torunn.bruland@ntnu.no.
  • 15 Clinic of Medicine, St. Olav's University Hospital, 7030 Trondheim, Norway. torunn.bruland@ntnu.no.
  • 16 Centre of Molecular Inflammation Research, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway. t.e.mollnes@medisin.uio.no.
  • 17 Department of Immunology, Oslo University Hospital and University of Oslo, 0372 Oslo, Norway. t.e.mollnes@medisin.uio.no.
  • 18 Research Laboratory, Department of Laboratory Medicine, Nordland Hospital, 8005 Bodo, Norway. t.e.mollnes@medisin.uio.no.
  • 19 K.G. Jebsen TREC, University of Tromsø, 9037 Tromsø, Norway. t.e.mollnes@medisin.uio.no.
  • 20 Centre of Molecular Inflammation Research, Norwegian University of Science and Technology (NTNU), 7030 Trondheim, Norway. arne.sandvik@ntnu.no.
  • 21 Department of Clinical and Molecular Medicine, NTNU, 7030 Trondheim, Norway. arne.sandvik@ntnu.no.
  • 22 Department of Gastroenterology and Hepatology, St. Olav's University Hospital, 7030 Trondheim, Norway. arne.sandvik@ntnu.no.
PMID: 30347808 DOI: 10.3390/ijms19103257
Abstract

The chemokine C-C motif ligand 20 (CCL20) is increased in the colonic mucosa during active inflammatory bowel disease (IBD) and can be found both in the epithelium and immune cells in the lamina propria. The present study investigated CCL20 and C-C motif Chemokine Receptor 6 (CCR6) in peripheral blood mononuclear cells (PBMCs) (n = 40) from IBD patients and healthy controls, to identify inductors of CCL20 release encountered in a local proinflammatory environment. CCL20 release from PBMCs was increased when activating TLR2/1 or NOD2, suggesting that CCL20 is part of a first line response to danger-associated molecular patterns also in immune cells. Overall, ulcerative colitis (UC) had a significantly stronger CCL20 release than Crohn's disease (CD) (+242%, p < 0.01), indicating that the CCL20-CCR6 axis may be more involved in UC. The CCL20 receptor CCR6 is essential for the chemotactic function of CCL20. UC with active inflammation had significantly decreased CCR6 expression and a reduction in CCR6⁺ cells in circulation, indicating chemoattraction of CCR6⁺ cells from circulation towards peripheral tissues. We further examined CCL20 induced release of cytokines from PBMCs. Stimulation with CCL20 combined with TNF increased IL-1β release from PBMCs. By attracting additional immune cells, as well as inducing proinflammatory IL-1β release from immune cells, CCL20 may protract the inflammatory response in ulcerative colitis.

Keywords

CCL20; CCR6; inflammatory bowel disease; interleukin-1β; peripheral blood mononuclear cells.

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