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

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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.

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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.

Disclosures

M. Kim and K. Lee have submitted an application for a patent on the use of the peptides to treat allergic diseases.

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Authors and Affiliations

  1. College of Pharmacy, Center for Cell Signalling & Drug Discovery Research, Ewha Womans University, Seoul, 120–750, South Korea

    Miyoung Kim, Jaehoon Jung, Youngjoo Kwon & Kyunglim Lee

  2. College of Medicine and Cancer Research Institute, Seoul National University, Seoul, 110–799, South Korea

    Junho Chung

  3. Department of Otorhinolaryngology–Head and Neck Surgery, Seoul National University College of Medicine, Seoul, 110–799, South Korea

    Chulhee Lee

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  1. Miyoung Kim
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  2. Junho Chung
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  3. Chulhee Lee
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  6. Kyunglim Lee
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Correspondence to Kyunglim Lee.

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Kim, M., Chung, J., Lee, C. et al. A peptide binding to dimerized translationally controlled tumor protein modulates allergic reactions. J Mol Med 89, 603–610 (2011). https://doi.org/10.1007/s00109-011-0740-8

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  • DOI: https://doi.org/10.1007/s00109-011-0740-8

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