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

本研究利用与炎性细胞因子受体结合的嵌合体多肽和与细胞膜无细胞毒活性的黏附序列，探讨了利用嵌合体多肽治疗炎症性疾病的可能性。作为预调查的结果，我们选择了肿瘤坏死因子α、TLR4和转化生长因子β1作为靶分子，并通过体外检测系统确定了各种拮抗肽和嵌合体多肽中最有希望的候选分子。通过嵌合体结合膜黏附序列，增强了肿瘤坏死因子α拮抗肽的抑制作用。气管内雾化吸入转化生长因子β1拮抗肽可降低博莱霉素性肺纤维化大鼠肺组织纤维化因子水平。

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.