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

作者：Kim Miyoung; Chung Junho; Lee Chulhee; Jung Jaehoon; Kwon Youngjoo; Lee Kyunglim^*

来源：Journal of Molecular Medicine-JMM, 2011, 89(6): 603-610.

DOI：10.1007/s00109-011-0740-8

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

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.

• 出版日期2011-6