Yoon Sun-Woo, Lee Chul-Ho, Kim Jeong-Yoon, Kim Jie-Youn, Sung Moon-Hee, Poo Haryoung
Mucosal Immunology Laboratory, BioNanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejon 305-600, Korea.
J Microbiol Biotechnol. 2008 Dec;18(12):1975-83.
The neuropeptide alpha-melanocyte-stimulating hormone (alpha- MSH) has anti-inflammatory property by downregulating the expressions of proinflammatory cytokines. Because alpha-MSH elicits the anti-inflammatory effect in various inflammatory disease models, we examined the therapeutic effect of oral administration of recombinant Lactobacillus casei, which secretes alpha-MSH (L. casei-alpha-MSH), on dextran sulfate sodium (DSS)-induced colitis in Balb/c mice. Thus, we constructed the alpha-MSH-secreting Lactobacillus casei by the basic plasmid, pLUAT-ss, which was composed of a PldhUTLS promoter and alpha-amylase signal sequence from Streptococcus bovis strain. Acute colitis was induced by oral administration of 5% DSS in drinking water for 7 days. To investigate the effect of L. casei-alpha-MSH on the colitis, L. casei or L. casei-alpha-MSH was orally administered for 7 days and their effects on body weight, mortality rate, cytokine production, and tissue myeloperoxidase (MPO) activity were observed. Administration of L. casei-alpha-MSH reduced the symptom of acute colitis as assessed by body weight loss (DSS alone: 14.45+/-0. 2 g; L. casei-alpha- MSH: 18.2+/-0.12 g), colitis score (DSS alone: 3.6+/-0.4; L. casei-alpha-MSH: 1.4+/-0.6), MPO activity (DSS alone: 42.7+/-4.5 U/g; L. casei-alpha-MSH: 10.25+/-0.5 U/g), survival rate, and histological damage compared with the DSS alone mice. L. casei-alpha-MSH-administered entire colon showed reduced in vitro production of proinflammatory cytokines and NF-kappaB activation. The alpha-MSH-secreting recombinant L. casei showed significant anti-inflammatory effects in the murine model of acute colitis and suggests a potential therapeutic role for this agent in clinical inflammatory bowel diseases.
神经肽α-黑素细胞刺激素（α-MSH）通过下调促炎细胞因子的表达而具有抗炎特性。由于α-MSH在各种炎症疾病模型中均能发挥抗炎作用，我们研究了口服分泌α-MSH的重组干酪乳杆菌（干酪乳杆菌-α-MSH）对葡聚糖硫酸钠（DSS）诱导的Balb/c小鼠结肠炎的治疗效果。因此，我们利用基本质粒pLUAT-ss构建了分泌α-MSH的干酪乳杆菌，该质粒由PldhUTLS启动子和来自牛链球菌菌株的α-淀粉酶信号序列组成。通过在饮用水中口服5% DSS 7天诱导急性结肠炎。为了研究干酪乳杆菌-α-MSH对结肠炎的影响，口服干酪乳杆菌或干酪乳杆菌-α-MSH 7天，并观察它们对体重、死亡率以及细胞因子产生和组织髓过氧化物酶（MPO）活性的影响。与仅给予DSS的小鼠相比，给予干酪乳杆菌-α-MSH可减轻急性结肠炎的症状，这通过体重减轻（仅DSS组：14.45±0.2 g；干酪乳杆菌-α-MSH组：18.2±0.12 g）、结肠炎评分（仅DSS组：3.6±0.4；干酪乳杆菌-α-MSH组：1.4±0.6）、MPO活性（仅DSS组：42.7±4.5 U/g；干酪乳杆菌-α-MSH组：- 10.25±0.5 U/g）、存活率和组织学损伤来评估。给予干酪乳杆菌-α-MSH的整个结肠显示促炎细胞因子的体外产生减少以及NF-κB激活减少。分泌α-MSH的重组干酪乳杆菌在急性结肠炎小鼠模型中显示出显著的抗炎作用，并提示该制剂在临床炎症性肠病中具有潜在的治疗作用。
