Billerey-Larmonier Claire, Uno Jennifer K, Larmonier Nicolas, Midura Anna J, Timmermann Barbara, Ghishan Fayez K, Kiela Pawel R
Department of Pediatrics, Steele Children's Research Center, University of Arizona Health Sciences Center, Tucson 85724, USA.
Inflamm Bowel Dis. 2008 Jun;14(6):780-93. doi: 10.1002/ibd.20348.
Curcumin (diferulolylmethane) has been shown to have a protective role in mouse models of inflammatory bowel diseases (IBD) 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.
We therefore investigated the effect of dietary curcumin in colitis induced in these 2 strains.
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 IC(50) 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.
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.
姜黄素（二阿魏酰甲烷）已被证明在炎症性肠病（IBD）小鼠模型中具有保护作用，并能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可行的支持性治疗选择。NKT缺陷的SJL/J小鼠中的三硝基苯磺酸（TNBS）结肠炎被描述为Th1介导的炎症，而BALB/c小鼠被认为表现出混合的Th1/Th2反应。
因此，我们研究了饮食中姜黄素对这两种品系诱导的结肠炎的影响。
在BALB/c小鼠中，姜黄素显著提高了生存率，防止了体重减轻，并使疾病活动恢复正常。在SJL/J小鼠中，姜黄素没有显示出保护作用。采用全基因组微阵列分析结肠基因表达，以确定姜黄素在这两种品系中的差异作用。该分析不仅证实了两种品系对姜黄素的不同反应，还表明对TNBS的反应不同。当用伴刀豆球蛋白A（ConA）在体外非特异性刺激时，姜黄素抑制了未免疫的BALB/c小鼠脾细胞的增殖，但不抑制SJL/J小鼠的脾细胞增殖。两种品系中CD4(+)脾细胞的增殖均受到抑制，尽管SJL/J小鼠中的半数抑制浓度（IC50）约高2倍。ConA显著增强了BALB/c小鼠而非SJL/J小鼠CD4(+)淋巴细胞分泌IL-4和IL-5的能力，而姜黄素将其分泌水平降低至对照水平。
饮食中姜黄素在TNBS结肠炎中的疗效在BALB/c和SJL/J小鼠品系中有所不同。尽管这些差异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免疫失调的性质而异。
