Basic research of new local treatment for inflammatory diseases using molecular-targeting chimera peptide

本研究以TNFα、TLR4和TGFβ1为靶分子，通过体外实验系统筛选出具有抗炎性细胞因子受体结合序列和细胞膜粘附序列的嵌合肽作为治疗炎症性疾病的有效靶分子。TNFα拮抗肽的抑制作用通过与膜粘附序列的嵌合体缀合而增强。肺内雾化吸入TGFβ1拮抗肽可降低博莱霉素诱导的肺纤维化大鼠模型肺组织中纤维化因子的水平。

We investigated the possibility of new powerful therapy for inflammatory diseases using chimera peptides that have a binding sequence to inflammatory cytokine receptors and an adhesion sequence to cell membrane without cytotoxic activity.As a result of pre-survey, we selected TNFα, TLR4, and TGFβ1 as the target molecules, and determined the promising candidates among various antagonist peptides and chimera peptides by the in vitro assay systems. Inhibitory effect of TNFα-antagonist peptide was increased by chimera conjugation with a membrane-adhesion sequence. Local treatment of TGFβ1-antagonist peptide by intratracheal nebulization decreased the levels of fibrotic factors in lung tissue in bleomycin-induced lung fibrosis rat model.