Identification of peptides that antagonize formyl peptide receptor-like 1-mediated signaling
SCIE
SCOPUS
- Title
- Identification of peptides that antagonize formyl peptide receptor-like 1-mediated signaling
- Authors
- Bae, YS; Lee, HY; Jo, EJ; Kim, JI; Kang, HK; Ye, RD; Kwak, JY; Ryu, SH
- Date Issued
- 2004-07-01
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Abstract
- Formyl peptide receptor-like 1 (FPRL1) is an important classical chemoattractant receptor that is expressed in phagocytic cells in the peripheral blood and brain. Recently, various novel agonists have been identified from several origins, such as host-derived molecules. Activation of FPRL1 is closely related to inflammatory responses in the host defense mechanism and neurodegenerative disorders. In the present study we identified several novel peptides by screening hexapeptide libraries that inhibit the binding of one of FPRL1's agonists (Trp-Lys-Tyr-Met-Val-D-Met-CONH2 (WKYMVm)) to its specific receptor, FPRL1, in RBL-2H3 cells. Among the novel peptides, Trp-Arg-Trp-Trp-Trp-Trp-CONH2 (WRWWWW (WRW4)) showed the most potent activity in terms of inhibiting WKYMVm binding to FPRL1. We also found that WRW4 inhibited the activation of FPRL1 by WKYMVm, resulting in the complete inhibition of the intracellular calcium increase, extracellular signal-regulated kinase activation, and chemotactic migration of cells toward WKYMVm. For the receptor specificity of WRW4 to the FPR family, we observed that WRW4 specif- ically inhibit the increase in intracellular calcium by the FPRL1 agonists MMK-1, amyloid beta42 (Abeta42) peptide, and F peptide, but not by the FPR agonist, fMLF. To investigate the effect-of WRW4 on endogenous FPRL1 ligand-induced cellular responses, we examined its effect on Abeta42 peptide in human neutrophils. Abeta42 peptide-induced superoxide generation and chemotactic 4 migration of neutrophils were inhibited by WRW4 which also completely inhibited the internalization of Abeta42 peptide in human macrophages. WRW4 is the first specific FPRL1 antagonist and is expected to be useful in the study of FPRL1 signaling and in the development of drugs against FPRL1-related diseases.
- Keywords
- PROTEIN-COUPLED RECEPTOR; PHOSPHOINOSITIDE HYDROLYSIS; CHEMOATTRACTANT RECEPTOR; CYCLOSPORINE-H; NEUTROPHIL ACTIVATION; CHEMOTACTIC AGONIST; HUMAN-LEUKOCYTES; CELL-LINES; POTENT; FPRL1
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/17856
- DOI
- 10.4049/jimmunol.173.1.607
- ISSN
- 0022-1767
- Article Type
- Article
- Citation
- JOURNAL OF IMMUNOLOGY, vol. 173, no. 1, page. 607 - 614, 2004-07-01
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