Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Paired Ig-Like Type 2 Receptor-Derived Agonist Ligands Ameliorate Inflammatory Reactions by Downregulating β1 Integrin Activity

  • Lee, Kyoung-Jin (Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University) ;
  • Lim, Dongyoung (Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University) ;
  • Yoo, Yeon Ho (Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University) ;
  • Park, Eun-Ji (Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University) ;
  • Lee, Sun-Hee (Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University) ;
  • Yadav, Birendra Kumar (Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University) ;
  • Lee, Yong-Ki (Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University) ;
  • Park, Jeong Hyun (Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University) ;
  • Kim, Daejoong (Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University) ;
  • Park, Kyeong Han (Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University) ;
  • Hahn, Jang-Hee (Department of Anatomy and Cell Biology, School of Medicine, Kangwon National University)
  • Received : 2016.04.01
  • Accepted : 2016.05.19
  • Published : 2016.07.31
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Abstract

The paired immunoglobulin-like type 2 receptor (PILR) family consists of two functionally opposite members, inhibitory $PILR{\alpha}$ and activating $PILR{\beta}$ receptors. PILRs are widely expressed in various immune cells and interact with their ligands, especially CD99 expressed on activated T cells, to participate in immune responses. Here we investigated whether PILR-derived agonists inhibit ${\beta}1$ integrin activity as ligands for CD99. PILR-derived peptides as well as PILR-Fc fusion proteins prevented cell adhesion to fibronectin through the regulation of ${\beta}1$ integrin activity. Especially, PILRpep3, a representative 3-mer peptide covering the conserved motifs of the PILR extracellular domain, prevented the clustering and activation of ${\beta}1$ integrin by dephosphorylating FAK and vinculin, which are major components of focal adhesion. In addition, PILRpep3 inhibited transendothelial migration of monocytes as well as endothelial cell tube formation. Furthermore, upon intraperitoneal injection of PILRpep3 into mice with collagen-induced arthritis, the inflammatory response of rheumatoid arthritis was strongly suppressed. Taken together, these results suggest that PILR-derived agonist ligands may prevent the inflammatory reactions of rheumatoid arthritis by activating CD99.

Keywords

References

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