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KMID : 0578320160390070557
Molecules and Cells
2016 Volume.39 No. 7 p.557 ~ p.565
Paired Ig-Like Type 2 Receptor-Derived Agonist Ligands Ameliorate Inflammatory Reactions by Downregulating ¥â1 Integrin Activity
Lee Kyoung-Jin

Lim Dong-Young
Yoo Yeon-Ho
Park Eun-Ji
Lee Sun-Hee
Yadav Birendra Kumar
Lee Yong-Ki
Park Jeong-Hyun
Kim Dae-Joong
Park Kyeong-Han
Hahn Jang-Hee
Abstract
The paired immunoglobulin-like type 2 receptor (PILR) family consists of two functionally opposite members, inhibitory PILR¥á and activating PILR¥â 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 ¥â1 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 ¥â1 integrin activity. Especially, PILRpep3, a representative 3-mer peptide covering the conserved motifs of the PILR extracellular domain, prevented the clustering and activation of ¥â1 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.
KEYWORD
¥â1 integrin, agonist ligands, CD99, inflammation, PILR
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