Institute of Drug Research, School of Pharmacy, Faculty of Medicine, Institute of Life Sciences, The Hebrew University, Jerusalem, Israel.
Peptides. 2011 Jan;32(1):125-30. doi: 10.1016/j.peptides.2010.10.026. Epub 2010 Nov 3.
Anti-inflammatory drugs are often of limited use due to low efficacy and toxic effects. The present study describes the anti-inflammatory effects of a novel nonapeptide termed IIIM1, using the mouse hind paw edema as an experimental model of inflammation. Multiple prophylactic injections of IIIM1 resulted in a significant reduction in carrageenan-induced foot pad swelling, both in mice and rats. A single prophylactic treatment of the peptide caused the maximal effect at 7-9 days between the initial peptide treatment and the subsequent carrageenan injection. A reduced inflammatory reaction was observed in transgenic mice constitutively expressing the peptide. A marked decrease in oxidative burst was observed in activated peritoneal macrophages obtained from peptide-treated mice. Furthermore, the sera of IIIM1-treated mice caused a significant decrease in the oxidative burst of macrophages. In addition, the reduction of hind paw swelling in mice injected with the sera of IIIM1-treated mice strongly suggests the presence of a circulating inducible factor responsible for the anti-inflammatory effect of the peptide. Previous LC/MS/MS analysis revealed the presence of a new peptide, termed RA1, in the sera of IIIM1-treated mice. RA1 was identified as a fragment of the Oryza Sativa Japonica protein. The anti-inflammatory effect of RA1 as evidenced by the reduction in carrageenan-induced hind paw swelling corresponded with the decrease in the oxidative burst of macrophages treated in vitro with this peptide. In conclusion, both IIIM1 and RA1 represent potential agents for the efficient treatment of inflammatory diseases that are currently incurable using presently available drugs.
抗炎药物由于疗效低和毒性作用往往用途有限。本研究描述了一种新型九肽 IIIM1 的抗炎作用，使用小鼠后爪水肿作为炎症的实验模型。多次预防性注射 IIIM1 可显著减少角叉菜胶诱导的足垫肿胀，无论是在小鼠还是大鼠中。肽的单次预防性治疗在初始肽治疗和随后的角叉菜胶注射之间的 7-9 天内达到最大效果。在持续表达该肽的转基因小鼠中观察到炎症反应减少。从肽处理的小鼠中获得的活化腹膜巨噬细胞中观察到氧化爆发明显减少。此外，肽处理小鼠的血清可显著降低巨噬细胞的氧化爆发。此外，注射 IIIM1 处理小鼠的血清后爪肿胀的减少强烈表明存在一种循环诱导因子，负责肽的抗炎作用。先前的 LC/MS/MS 分析显示，在 IIIM1 处理小鼠的血清中存在一种新的肽，称为 RA1。RA1 被鉴定为水稻蛋白的片段。RA1 的抗炎作用通过减少角叉菜胶诱导的后爪肿胀来证明，这与用该肽体外处理的巨噬细胞氧化爆发减少相对应。总之，III M1 和 RA1 均代表目前可用药物无法治愈的炎症性疾病的有效治疗的潜在药物。
