Protective effect of Clostridium tyrobutyricum in acute dextran sodium sulphate-induced colitis: differential regulation of tumour necrosis factor-α and interleukin-18 in BALB/c and severe combined immunodeficiency mice
Protective effect of Clostridium tyrobutyricum in acute dextran sodium sulphate-induced colitis: differential regulation of tumour necrosis factor-α and interleukin-18 in BALB/c and severe combined immunodeficiency mice
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DOI：
10.1111/j.1365-2249.2011.04498.x
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发表时间：
2012-02-01
影响因子：
4.6
通讯作者：
Kozakova, H.
中科院分区：
文献类型：
--
作者：
Hudcovic, T.;Kolinska, J.;Kozakova, H.
溃疡性结肠炎的治疗中有希望的方法之一是将丁酸盐（结肠细胞的能量来源）施用到结肠腔中。本研究探讨丁酸产生菌酪丁酸梭菌对葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎的影响。免疫活性的BALB/c和免疫缺陷的严重联合免疫缺陷（SCID）小鼠在无特异性病原体（SPF）条件下饲养。在诱导DSS结肠炎前1周和口服DSS治疗期间，无C的DSS的管理。酪丁酸治疗导致临床症状出血、直肠脱垂和结肠炎诱导的抗原CD 11b（固有层中浸润炎性细胞的标记物）增加的出现。如通过DSS处理7天后的组织学损伤评分和结肠缩短所判断的，BALB/c和SCID小鼠中结肠炎的严重程度相似。两种品系的小鼠也显示出紧密连接（TJ）蛋白封闭小带（ZO）-1表达和MUC-2粘蛋白抑制的类似减少。观察到SCID小鼠结肠中细胞因子肿瘤坏死因子（TNF）-α和BALB/c小鼠中白细胞介素（IL）-18水平高度升高。C. Tyrobutyricum预防了DSS-结肠炎的临床症状的出现，恢复了正常的MUC-2产生，TJ蛋白ZO-1的表达不变，并且分别降低了SCID和BALB/c小鼠降结肠中TNF-α和IL-18的水平。这些特征中的一些可归因于结肠腔中丁酸盐的产生增加及其在保护屏障功能和调节IL-18表达中的作用。
One of the promising approaches in the therapy of ulcerative colitis is administration of butyrate, an energy source for colonocytes, into the lumen of the colon. This study investigates the effect of butyrate producing bacterium Clostridium tyrobutyricum on dextran sodium sulphate (DSS)-induced colitis in mice. Immunocompetent BALB/c and immunodeficient severe combined immunodeficiency (SCID) mice reared in specific-pathogen-free (SPF) conditions were treated intrarectally with C. tyrobutyricum 1 week prior to the induction of DSS colitis and during oral DSS treatment. Administration of DSS without C. tyrobutyricum treatment led to an appearance of clinical symptoms bleeding, rectal prolapses and colitis-induced increase in the antigen CD11b, a marker of infiltrating inflammatory cells in the lamina propria. The severity of colitis was similar in BALB/c and SCID mice as judged by the histological damage score and colon shortening after 7 days of DSS treatment. Both strains of mice also showed a similar reduction in tight junction (TJ) protein zonula occludens (ZO)-1 expression and of MUC-2 mucin depression. Highly elevated levels of cytokine tumour necrosis factor (TNF)-a in the colon of SCID mice and of interleukin (IL)-18 in BALB/c mice were observed. Intrarectal administration of C. tyrobutyricum prevented appearance of clinical symptoms of DSS-colitis, restored normal MUC-2 production, unaltered expression of TJ protein ZO-1 and decreased levels of TNF-a and IL-18 in the descending colon of SCID and BALB/c mice, respectively. Some of these features can be ascribed to the increased production of butyrate in the lumen of the colon and its role in protection of barrier functions and regulation of IL-18 expression.