Protective effects of dietary curcumin in mouse model of chemically induced colitis are strain dependent
Protective effects of dietary curcumin in mouse model of chemically induced colitis are strain dependent
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DOI：
10.1002/ibd.20348
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发表时间：
2008-06-01
影响因子：
4.9
通讯作者：
Kiela, Pawel R.
中科院分区：
文献类型：
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作者：
Billerey-Larmonier, Claire;Uno, Jennifer K.;Kiela, Pawel R.
背景：姜黄素(二阿魏酸甲烷)已被证明在炎症性肠病小鼠模型中具有保护作用(11313)，并可降低人类溃疡性结肠炎(UC)的复发率，因此使其成为一种潜在的可行的支持性治疗方案。NKT基因缺陷的SJL/J小鼠的三硝基苯磺酸(TNBS)结肠炎一直被认为是Th1介导的炎症，而BALB/c小鼠则表现出混合的Th1/Th2反应。方法：因此，我们研究了饮食中姜黄素对这两个品系诱导的结肠炎的影响。结果：在BALB/c小鼠中，姜黄素显著增加了存活率，防止了体重减轻，并使疾病活动正常化。在SJL/J小鼠中，姜黄素没有显示出保护作用。用全基因组芯片分析结肠基因的表达，以确定姜黄素在这两个菌株中的差异作用。这一分析不仅证实了这两个菌株对姜黄素的不同反应，而且也表明了对TNBS的不同反应。用刀豆蛋白A(ConA)体外非特异性刺激时，姜黄素可抑制幼龄BALB/c小鼠脾细胞的增殖，但对SJL/J小鼠的增殖无明显影响。两个品系的CD4(+)脾细胞的增殖都受到抑制，尽管SJL/J小鼠的IC50大约高出2倍。姜黄素可显著促进BALB/c小鼠和SJL/J小鼠外周血中CD4(+)淋巴细胞分泌IL-4和IL-5，姜黄素可使其降低至对照水平。结论：膳食姜黄素治疗TNBS结肠炎的疗效因品系而异。尽管这些差异背后的确切机制尚不清楚，但结果表明，饮食中姜黄素的治疗价值可能因IBD免疫失调的性质而不同。
Background: Curcumin (diferulolylmethane) has been shown to have a protective role in mouse models of inflammatory bowel diseases (11313) and to reduce the relapse rate in human ulcerative colitis (UC), thus making it a potentially viable supportive treatment option. Trinitrobenzene sulfonic acid (TNBS) colitis in NKT-deficient SJL/J mice has been described as Th1-mediated inflammation, whereas BALB/c mice are believed to exhibit a mixed Th1/Th2 response.Methods: We therefore investigated the effect of dietary curcumin in colitis induced in these 2 strains.Results: In the BALB/c mice, curcumin significantly increased survival, prevented weight loss, and normalized disease activity. In the SJL/J mice, curcumin demonstrated no protective effects. Genomewide microarray analysis of colonic gene expression was employed to define the differential effect of curcumin in these 2 strains. This analysis not only confirmed the disparate responses of the 2 strains to curcumin but also indicated different responses to TNBS. Curcumin inhibited proliferation of splenocytes from naive BALB/c mice but not SJL/J mice when nonspecifically stimulated in vitro with concanavalin A (ConA). Proliferation of CD4(+) splenocytes was inhibited in both strains, albeit with about a 2-fold higher IC50 in SJL/J mice. Secretion of IL-4 and IL-5 by CD4(+) lymphocytes of BALB/c mice but not SJL/J mice was significantly augmented by ConA and reduced to control levels by curcumin.Conclusions: The efficacy of dietary curcumin in TNBS colitis varies in BALB/c and SJL/J mouse strains. Although the exact mechanism underlying these differences is unclear, the results suggest that the therapeutic value of dietary curcumin may differ depending on the nature of immune dysregulation in IBD.