SCRG1 Suppresses LPS-induced CCL22 Production Through ERK1/2 Activation in Mouse Macrophage Raw264.7 Cells

Mol Med Rep. 2017 Jun;15(6):4069-4076. doi: 10.3892/mmr.2017.6492. Epub 2017 Apr 20.

Abstract

Recently, we identified the scrapie responsive gene 1 (SCRG1) secreted from mesenchymal stem cells (MSCs) and its receptor bone marrow stromal cell antigen 1 (BST1) as positive regulators of stem cell qualities such as self‑renewal, migration abilities, and osteogenic differentiation potential. Here, we examined the effect of the paracrine activity of SCRG1 in macrophages. The mouse macrophage‑like cell line Raw264.7 expressed BST1/β1 or BST1/β2 integrin as possible SCRG1 receptors. Unexpectedly, recombinant SCRG1 did not enhance cell proliferation, migration, or adhesion in these macrophages. However, further examination of the effect of SCRG1 in Raw264.7 cells did reveal a potent anti‑inflammatory effect whereby SCRG1 suppressed LPS‑induced CCL22 production. SCRG1 also induced the phosphorylation of extracellular signal‑regulated kinase 1/2 (ERK1/2) in these cells and, moreover, a mitogen‑activated protein kinase (MAPK)/ERK kinase inhibitor U0126 significantly suppressed the effect of SCRG1 on LPS‑induced chemokine CCL22 production. Taken together, these data indicate that SCRG1 signals through the MAPK pathway and suppresses the LPS signaling pathway. CCL22 is generally known to be chemotactic for monocytes, dendritic cells, natural killer cells and chronically activated T lymphocytes, suggesting that MSC‑derived SCRG1 may block infiltration of these cells. A mechanism is proposed by which MSCs play their immunosuppressive role through suppressing chemokine expression in monocyte/macrophage lineage cells.

MeSH terms

  • ADP-ribosyl Cyclase / genetics
  • ADP-ribosyl Cyclase / metabolism
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • CD18 Antigens / genetics
  • CD18 Antigens / metabolism
  • Cell Adhesion
  • Cell Movement
  • Cell Proliferation
  • Chemokine CCL22 / biosynthesis*
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism
  • Lipopolysaccharides / immunology*
  • Macrophages / immunology*
  • Macrophages / metabolism*
  • Mice
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Phosphorylation
  • RAW 264.7 Cells

Substances

  • Antigens, CD
  • CD18 Antigens
  • Chemokine CCL22
  • GPI-Linked Proteins
  • Integrin beta1
  • Lipopolysaccharides
  • Nerve Tissue Proteins
  • Scrg1 protein, mouse
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • ADP-ribosyl Cyclase
  • ADP-ribosyl cyclase 2