TY - JOUR
T1 - A peptide binding to dimerized translationally controlled tumor protein modulates allergic reactions
AU - Kim, Miyoung
AU - Chung, Junho
AU - Lee, Chulhee
AU - Jung, Jaehoon
AU - Kwon, Youngjoo
AU - Lee, Kyunglim
N1 - 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.
PY - 2011/6
Y1 - 2011/6
N2 - 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.
AB - 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.
KW - Anti-allergic peptide
KW - Asthma
KW - Biochemistry
KW - Drug development
KW - dTCTP
KW - Eosinophil infiltration
KW - Peptide libraries
KW - Phage-displayed 7-mer peptide
KW - Rhinitis model
UR - http://www.scopus.com/inward/record.url?scp=79959955190&partnerID=8YFLogxK
U2 - 10.1007/s00109-011-0740-8
DO - 10.1007/s00109-011-0740-8
M3 - Article
C2 - 21384150
AN - SCOPUS:79959955190
SN - 0946-2716
VL - 89
SP - 603
EP - 610
JO - Journal of Molecular Medicine
JF - Journal of Molecular Medicine
IS - 6
ER -