Receptor-Type Protein-Tyrosine Phosphatase ζ and Colony Stimulating Factor-1 Receptor in the Intestine: Cellular Expression and Cytokine- and Chemokine Responses by Interleukin-34 and Colony Stimulating Factor-1

PLoS One. 2016 Nov 29;11(11):e0167324. doi: 10.1371/journal.pone.0167324. eCollection 2016.

Abstract

Differential intestinal expression of the macrophage growth factors colony stimulating factor-1 (CSF-1), interleukin (IL)-34, and their shared CSF-1 receptor (CSF-1R) in inflammatory bowel disease (IBD) has been shown. Diverse expression between CSF-1 and IL-34, suggest that IL-34 may signal via an alternate receptor. Receptor-type protein-tyrosine phosphatase ζ (PTPRZ1, RPTP-ζ), an additional IL-34 receptor, was recently identified. Here, we aimed to assess PTPRZ1 expression in IBD and non-IBD intestinal biopsies. Further, we aimed to investigate cellular PTPRZ1 and CSF-1R expression, and cytokine- and chemokine responses by IL-34 and CSF-1. The expression of PTPRZ1 was higher in non-IBD colon compared to ileum. PTPRZ1 expression was not altered with inflammation in IBD, however, correlated to IL34, CSF1, and CSF1R. The expression patterns of PTPRZ1 and CSF-1R differed in peripheral blood mononuclear cells (PBMCs), monocytes, macrophages, and intestinal epithelial cell line. PBMCs and monocytes of the same donors responded differently to IL-34 and CSF-1 with altered expression of tumor-necrosis factor α (TNF-α), IL-1β, interferon γ (IFN-γ), IL-13, IL-8, and monocyte chemotactic protein-1 (MCP-1) levels. This study shows that PTPRZ1 was expressed in bowel tissue. Furthermore, CSF-1R protein was detected in an intestinal epithelial cell line and donor dependently in primary PBMCs, monocytes, and macrophages, and first hints also suggest an expression in these cells for PTPRZ1, which may mediate IL-34 and CSF-1 actions.

MeSH terms

  • Case-Control Studies
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Chemokines / analysis
  • Chemokines / genetics
  • Chemokines / metabolism*
  • Colon / metabolism
  • Cytokines / analysis
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression / drug effects
  • Humans
  • Ileum / metabolism
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / pathology
  • Interleukins / metabolism*
  • Interleukins / pharmacology
  • Intestinal Mucosa / metabolism*
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Macrophage Colony-Stimulating Factor / metabolism*
  • Macrophage Colony-Stimulating Factor / pharmacology
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Monocytes / cytology
  • Monocytes / drug effects
  • Monocytes / metabolism
  • RNA, Messenger / metabolism
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5 / metabolism*
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*

Substances

  • Chemokines
  • Cytokines
  • IL34 protein, human
  • Interleukins
  • RNA, Messenger
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • Macrophage Colony-Stimulating Factor
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5

Grants and funding

This work was supported by grants from the Swedish Research Council (523-2012-2480 to EAB), Stockholm County Council/ ALF project (20140367 to EAB), Karolinska Institutet Funds (EAB), Åke Wiberg Foundation (EAB) and the Ihre Foundation (SA). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.