2. Academic Validation
  3. Dipeptide HCH6-1 inhibits neutrophil activation and protects against acute lung injury by blocking FPR1

Dipeptide HCH6-1 inhibits neutrophil activation and protects against acute lung injury by blocking FPR1

  • Free Radic Biol Med. 2017 May;106:254-269. doi: 10.1016/j.freeradbiomed.2017.02.038.
Shun-Chin Yang 1,  Shih-Hsin Chang 2,  Pei-Wen Hsieh 3,  Yin-Ting Huang 4,  Chiu-Ming Ho 5,  Yung-Fong Tsai 6,  Tsong-Long Hwang 7
Affiliations

Affiliations

  • 1 Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Department of Anesthesiology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei 112, Taiwan; Division of Natural Products, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
  • 2 Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Research Center for Industry of Human Ecology, Research Center for Chinese Herbal Medicine, and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan.
  • 3 Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Division of Natural Products, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Research Center for Industry of Human Ecology, Research Center for Chinese Herbal Medicine, and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan; Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan; Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
  • 4 Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
  • 5 Department of Anesthesiology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei 112, Taiwan.
  • 6 Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
  • 7 Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Division of Natural Products, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Research Center for Industry of Human Ecology, Research Center for Chinese Herbal Medicine, and Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan; Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan; Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan. Electronic address: htl@mail.cgu.edu.tw.
PMID: 28232203 DOI: 10.1016/j.freeradbiomed.2017.02.038
Abstract

Formyl peptide receptor 1 (FPR1) is an emerging therapeutic target for the discovery of drugs to treat neutrophilic inflammatory diseases. However, development of FPR1 antagonists for clinical use is still inadequate. The purpose of this study was to identify a synthetic dipeptide N-(N-benzoyl-L-tryptophanyl)-D-phenylanlanine methyl ester (HCH6-1) as a FPR1 inhibitor and to investigate its protective effects against acute lung injury (ALI). HCH6-1 inhibited superoxide anion generation, Elastase release, and chemotaxis in human neutrophils specifically activated by formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLF), an FPR1 agonist. HCH6-1 produced right shifts in the concentration-response curves of fMLF, suggesting that HCH6-1 was a competitive antagonist of FPR1. Indeed, HCH6-1 bound to FPR1 in human neutrophils and neutrophil-like THP-1 as well as hFPR1-transfected HEK293 cells. Also, the FPR1 downstream signaling pathways were competitively inhibited by HCH6-1. Furthermore, HCH6-1 prevented pulmonary neutrophil infiltration and edema along with alveolar damage in LPS-induced ALI in mice. Our findings suggest that HCH6-1, a FPR1 antagonist, may have potential as a new therapeutic agent for treating FPR1-involved inflammatory lung diseases.

Keywords

Chemotaxis; Elastase; Formyl peptide receptor 1; HCH6-1; Neutrophil; Superoxide anion.

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