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A novel phage-displayed peptide (PAP5) potentiates TLR2-mediated cytokine expression and innate immune response
- Author(s)
- NGUYEN THI HUYEN TRANG
- Advisor
- Sangdun Choi
- Department
- 일반대학원 분자과학기술학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2021-02
- Language
- kor
- Keyword
- Pam3CSK 4; Toll-like receptor 2; agonist; ischemic stroke; peptide; phage display; vaccine adjuvant
- Alternative Abstract
- Toll-like receptor 2 (TLR2), together with its two co-receptors TLR1 and TLR6, plays a significant role in the protection of host immunity through the secretion of pro-inflammatory cytokines. Occasionally, the traditional activation of TLR2 is inefficient in neutralizing the surge of pathogenic invasion; thus, the utilization of therapeutic activators for a sustained and balanced immune response becomes necessary. Here, employing a library of phage-displayed 12-mer random peptides, we identified a completely unique sequence (herein mentioned as PAP5) that specifically invokes TLR1/2-mediated downstream signaling, which might be blocked by pretreatment with a TLR1/2 antagonist. PAP5 remarkably induced the phosphorylation of mitogen-activated protein kinases (MAPKs) and activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in RAW 264.7 cells. We showed that PAP5 upregulated NF-κB-mediated expression of TNF-α and IL-6 in both mouse and human THP-1 macrophages. Altogether, our results suggest that PAP5 binds to the extracellular domains of both TLR1 and TLR2, thus facilitating TLR1/2 heterodimerization and downstream signal transduction. The peptide showed markedly specificity towards the activation of TLR1/2-mediated downstream signaling without affecting other TLR signaling pathways. We envision that PAP5 might be an appropriate candidate for the development of a potent vaccine adjuvant and antitumor agent or a drug to stop ischemic stroke from white matter. Our data demonstrate the usefulness of a phage-displayed peptide library-based high-throughput screening in the development of novel peptides as anticancer agents, vaccine adjuvants or monotherapy drugs to treat various TLR2-associated diseases.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Molecular Science and Technology > 3. Theses(Master)
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