Effects of lauric acid on the production of pro-inflammatory mediators and its risk assessment

月桂酸（LA）是一种C-12天然脂肪酸，最近报道其在巨噬细胞中诱导关键炎性转录因子NF κ B及其靶基因之一环氧合酶（考克斯-2）的活性。考克斯-2是目前公认的炎症和炎症相关的致癌作用的发病的核心球员。然而，其对促炎细胞因子产生的影响以及体内风险评估尚未确定。在本研究中，我们发现LA增加了小鼠腹腔巨噬细胞中IL（白细胞介素）-1 β、MIF（巨噬细胞移动抑制因子）和IL-6的产生，但不增加TNF（肿瘤坏死因子）-α的产生。在小鼠耳部炎症试验中，LA不诱导高达TPA的1000倍剂量的炎症，TPA用作阳性对照，并且也不显著上调考克斯-2 mRNA表达。然后，LA进行结肠癌的短期模型，其中异常隐窝病灶（ACF）被用作组织学肿瘤标志物。氧化偶氮甲烷（AOM）和葡聚糖硫酸钠（DSS）分别被用作肿瘤引发剂和促进剂。与阳性对照组（AOM+DSS）相比，在基础饲料中以1%的剂量口服LA 10周，倾向于降低体重和结肠直肠长度（结肠炎症的标志物），并增加肝脏重量，表明LA的副作用。另一方面，ACF的形成，肾脏和脂肪组织的重量在这些组之间没有显著变化。总之，尽管首次发现LA可增强体外和体内的一些促炎生物标志物，但LA有害作用的确切证据仍有待确定，因此在不久的将来需要进一步努力解决这些问题。

Lauric acid (LA), a C-12 natural fatty acid, has recently been reported to induce the activity of a pivotal inflammatory transcription factor, NFkappaB, and one of its target genes, cyclooxygenase (COX-2), in macrophages. COX-2 is now recognized as a central player in the onset of inflammation and inflammation-associated carcinogenesis. However, its effects on pro-inflammatory cytokine production as well as in vivo risk assessment are yet to be determined. In the present study, we found that LA increased the production of IL (interleukin)-1beta, MIF (macrophage migration inhibitory factor), and IL-6, but not TNF (tumor necrosis factor)-alpha, in mouse peritoneal macrophages. In the mouse ear inflammation test, LA did not induce inflammation up to 1000-fold dose to TPA, which was used as a positive control, and also did not significantly up-regulate COX-2 mRNA expression. Then, LA was subjected to a short-term model for colon cancer, in which aberrant crypt foci (ACF) was employed as a histological tumor marker. Azoxymethane (AOM) and dextran sulfate sodium (DSS) were used as the tumor initiator and promoter, respectively. Oral feeding of LA at a dose of 1% in the basal diet for 10 weeks tended to decrease body weight and colorectal length (a maker for colonic inflammation) and to increase liver weight as compared with positive control (AOM+DSS), suggesting the side-effect of LA. On the other hand, the formation of ACF, the weights of kidney and fatty tissues did not markedly changed between those groups. In conclusion, although LA was revealed, for the first time, to enhance some pro-inflammatory biomarkers both in vitro and in vivo, definitive evidence of harmful effects of LA remain to be identified, and thus further efforts for addressing those issues will be warranted in the near future.