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Publications

Journal Article Research Support, Non-U.S. Gov't Epublish 5 citations

PubMed: 38334630 DOI: 10.3390/cells13030238

Pro-Fibrotic Effects of CCL18 on Human Lung Fibroblasts Are Mediated via CCR6.

Cells 13(3)

Authors: Kerstin Höhne, Annett Wagenknecht, Corinna Maier, Peggy Engelhard, Torsten Goldmann, Stephan J Schließmann, Till Plönes, Martin Trepel, Hermann Eibel, Joachim Müller-Quernheim, Gernot Zissel

Affiliations

  • Department of Pneumology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.
  • Department of Medicine I, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.
  • Histology, Research Center Borstel, 23845 Borstel, Germany.
  • Department of Pneumology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany. Integrative and Experimental Exercise Science and Training, Institute of Sport Science, University of Würzburg, 97082 Würzburg, Germany.
  • Department of Thoracic Surgery, Center for Surgery, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.
  • Department of Internal Medicine II, University Medical Center and Medical Faculty, Augsburg University, Germany Internal Medicine and Oncology, Faculty of Medicine, University of Augsburg, 86156 Augsburg, Germany.
  • Center for Chronic Immunodeficiency, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.

Abstract

BACKGROUND

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown origin, with a median patient survival time of ~3 years after diagnosis without anti-fibrotic therapy. It is characterized by progressive fibrosis indicated by increased collagen deposition and high numbers of fibroblasts in the lung. It has been demonstrated that CCL18 induces collagen and αSMA synthesis in fibroblasts. We aimed to identify the CCL18 receptor responsible for its pro-fibrotic activities.

METHODS

We used a random phage display library to screen for potential CCL18-binding peptides, demonstrated its expression in human lungs and fibroblast lines by PCR and immunostaining and verified its function in cell lines.

RESULTS

We identified CCR6 (CD196) as a CCL18 receptor and found its expression in fibrotic lung tissue and lung fibroblast lines derived from fibrotic lungs, but it was almost absent in control lines and tissue. CCL18 induced receptor internalization in a CCR6-overexpressing cell line. CCR6 blockade in primary human lung fibroblasts reduced CCL18-induced FGF2 release as well as collagen-1 and αSMA expression. Knockdown of CCR6 in a mouse fibroblast cell line abolished the induction of collagen and α-smooth muscle actin expression.

CONCLUSION

Our data indicate that CCL18 triggers pro-fibrotic processes via CCR6, highlighting its role in fibrogenesis.

MeSH

Collagen, Cells, Cell Line, Lung, Idiopathic Pulmonary Fibrosis, Fibroblasts, Tissues

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