Kannengiesser Klaus, Maaser Christian, Heidemann Jan, Luegering Andreas, Ross Matthias, Brzoska Thomas, Bohm Markus, Luger Thomas A, Domschke Wolfram, Kucharzik Torsten
Department of Medicine B, University of Muenster, Muenster, Germany.
Inflamm Bowel Dis. 2008 Mar;14(3):324-31. doi: 10.1002/ibd.20334.
Despite some progress in recent years, the options for treating inflammatory bowel disease (IBD) are still dissatisfying, and surgery rates are still high. The anti-inflammatory effects of melanocortin peptides such as alpha-melanocyte-stimulating hormone (alpha-MSH) have been described recently in, for example, dextran sodium sulfate (DSS) colitis in mice. The aim of this study was to investigate the therapeutic potential of the melanocortin-derived tripeptide alpha-MSH(11-13) (KPV) and its mode of action in 2 models of intestinal inflammation.
The anti-inflammatory activity of KPV was analyzed in 2 well-described models of IBD: DSS colitis, and CD45RB(hi) transfer colitis. Furthermore, animals expressing a nonfunctional melanocortin-1 receptor (MC1Re/e) received DSS for induction of colitis and were treated with KPV. The course of inflammation was monitored by weight loss and histological changes in the colon as well as by myeloperoxidase (MPO) activity.
In the DSS-colitis model, treatment with KPV led to earlier recovery and significantly stronger regain of body weight. Histologically, inflammatory infiltrates were significantly reduced in KPV-treated mice, which was confirmed by the significant reduction of MPO activity in colonic tissue after KPV treatment. Supporting these findings, KPV treatment of transfer colitis led to recovery, regain of body weight, and reduced inflammatory changes histologically. In MC1Re/e mice, KPV treatment rescued all animals in the treatment group from death during DSS colitis.
The melanocortin-derived tripeptide KPV showed significant anti-inflammatory effects in 2 murine models of colitis. These effects seem to be at least partially independent of MC1R signaling. In conclusion, our data suggest KPV as an interesting therapeutic option for the treatment of IBD.
尽管近年来取得了一些进展，但炎症性肠病（IBD）的治疗选择仍然不尽人意，手术率仍然很高。黑素皮质素肽如α-黑素细胞刺激素（α-MSH）的抗炎作用最近已在例如小鼠葡聚糖硫酸钠（DSS）结肠炎中得到描述。本研究的目的是研究黑素皮质素衍生的三肽α-MSH(11-13)（KPV）在两种肠道炎症模型中的治疗潜力及其作用方式。
在两种已充分描述的IBD模型中分析KPV的抗炎活性：DSS结肠炎和CD45RB(hi)转移结肠炎。此外，表达无功能黑素皮质素-1受体（MC1Re/e）的动物接受DSS诱导结肠炎，并接受KPV治疗。通过体重减轻、结肠组织学变化以及髓过氧化物酶（MPO）活性监测炎症进程。
在DSS结肠炎模型中，KPV治疗导致更早恢复和显著更强的体重恢复。组织学上，KPV治疗的小鼠炎症浸润显著减少，KPV治疗后结肠组织中MPO活性显著降低证实了这一点。支持这些发现的是，KPV治疗转移结肠炎导致恢复、体重恢复以及组织学上炎症变化减少。在MC1Re/e小鼠中，KPV治疗使治疗组的所有动物在DSS结肠炎期间免于死亡。
黑素皮质素衍生的三肽KPV在两种小鼠结肠炎模型中显示出显著的抗炎作用。这些作用似乎至少部分独立于MC1R信号传导。总之，我们的数据表明KPV是治疗IBD的一个有吸引力的治疗选择。
