A peptide binding to dimerized translationally controlled tumor protein modulates allergic reactions

Miyoung Kim, Junho Chung, Chulhee Lee, Jaehoon Jung, Youngjoo Kwon, Kyunglim Lee

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Translationally controlled tumor protein (TCTP) is believed to be involved in a variety of inflammatory processes: secretion of histamine and cytokines such as IL-4, IL-8, IL-13, and granulocyte/macrophage colony-stimulating factor; chemoattraction for eosinophils; augmentation of B cell proliferation; and immunoglobulin production, thereby potentially regulating allergic phenomena. In a previous study, we showed that the cytokine-releasing activity of extracellular TCTP is generated only when TCTP dimerizes via the intermolecular disulfide bond of NH2-terminal truncated TCTP implying that the dimerized TCTP (dTCTP) promotes the inflammatory phenomena. Modulation of dTCTP, thus, may offer a strategy for the treatment of chronic allergic diseases. In this study, we searched for dTCTP-binding peptides (dTBPs) by screening a phage-displayed 7-mer peptide library. We identified one peptide in the library, designated as dTBP2, which showed higher affinity to dTCTP than to full-length, monomeric TCTP. dTBP2 inhibited the induction of IL-8 by dTCTP from BEAS-2B cells. dTBP2 also reduced symptom score and eosinophil infiltration in a mouse rhinitis model. This study suggests that the dTBP2 binding to dTCTP modulates the release of inflammatory mediators of dTCTP. This result may provide a rational strategy for the treatment of allergic diseases.

Original languageEnglish
Pages (from-to)603-610
Number of pages8
JournalJournal of Molecular Medicine
Volume89
Issue number6
DOIs
StatePublished - Jun 2011

Bibliographical note

Funding Information:
Acknowledgments This study was supported by a grant of the Korea Healthcare technology R&D Project, Ministry for Health, Welfare & Family Affairs (A090030), Mid-career Research Program through NRF grant funded by the MEST (R01-2007-000-20263-0), Seoul R&BD Program (ST090801), and the NCRC program of MOST/KOSEF (R15-2006-020) to Kyunglim Lee, Ewha Womans University (2010) to Miyoung Kim, and William F. Milton Fund to Guido Guidotti.

Keywords

  • Anti-allergic peptide
  • Asthma
  • Biochemistry
  • Drug development
  • dTCTP
  • Eosinophil infiltration
  • Peptide libraries
  • Phage-displayed 7-mer peptide
  • Rhinitis model

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