In this study, we investigated the impact of TLE on LPS signaling in vitro and in experimental colitis. TLE prevented LPS-induced NF-κB activity both in IEC-18 cells and splenocytes through blockade of IκBα degradation, RelA nuclear translocation and transcriptional activity. TLE comprised of numerous components including vitamin C, polyphenols and carotenoids. Though our study has not directly identified the active ingredients responsible for this effect, TLE-mediated inhibition of NF-κB activity was replicated using pure lycopene (data not shown). Therefore this carotenoid is at least partially responsible for this inhibitory activity.
Despite its inhibitory effect in vitro, DSS-induced acute colitis was exacerbated in TLE fed NF-κBEGFP
mice. Mice fed with a TLE rich diet and exposed to DSS lost more weight than mice fed the control diet. This weight loss was not observed in non DSS treated fed TLE, indicating that the diet alone is not responsible for the phenotype. Fluorescent macro-imaging of the colon of TLE-fed, DSS-exposed NF-κBEGFP
mice showed a strong increase in EGFP expression compared to control diet mice, indicating enhanced NF-κB activity in these mice. Of note, EGFP expression was not increased in control diet-fed, DSS-exposed mice at d 4, which correlated with minimal weight loss. In contrast, increased EGFP expression in TLE-fed, DSS-exposed NF-κBEGFP
mice correlated with pronounced weight loss and histological evidence of intestinal damage. Moreover, increased levels of the NF-κB dependent genes IL-6, TNFα and MCP-1 were detected in TLE-fed, DSS-exposed NF-κBEGFP
mice. Consequently, exacerbated colitis correlated with enhanced NF-κB activation and pro-inflammatory gene expression in TLE-fed, DSS-exposed NF-κBEGFP
mice. The 2% diet utilized in this study corresponds to 12 mg lycopene/day. This amount falls within the range comsumed in a typical human diet, with for example, spaghetti sauce (21 mg/serving), watermelon (11 mg/serving), tomatoes (14 mg/serving) and tomato juice (19 mg/serving) providing from 10–40 mg of the phytochemical 
The deleterious effect of TLE on DSS-induced colitis is likely specific to the model on intestinal injury. Indeed bacteria-induced EGFP expression was reduced in TLE-fed IL-10−/−
mice compared to control diet fed mice, with a concomitant attenuation of cecal and proximal colonic inflammation. These findings suggest that the deleterious effects of TLE relates to the injury-based mechanism of the DSS model, which cause disruption of the epithelial cell layer resulting in breakdown of intestinal barrier function. This breach of barrier function would likely result in increased uptake of luminal antigens (bacteria and bacterial products) as well as activation of lamina propria immune cells and inflammatory response 
. This hypothesis reconciles the apparent discordance between enhanced NF-κB activation in the colon of TLE-fed, DSS exposed mice and the inhibitory action of the phytochemical in vitro and in the IL-10−/−
NF-κB drives expression of target genes that function to protect IEC from signal-induced apoptosis as well as promoting restitution of the epithelium 
. A potential explanation for exacerbated colitis in TLE-treated, DSS-exposed mice may be that TLE impair barrier function thereby increasing the susceptibility of IEC to undergo apoptosis. This possibility is supported by our immunohistochemical and western blot analysis showing that the colon of TLE-fed mice displayed enhanced caspase-3 processing. Increased caspase-3 processing has been previously associated with DSS-induced colonic tissue damage and colitis 
. Furthermore, higher number of TUNEL positive IEC were observed in TLE-fed, DSS-exposed mice. In contrast, the number of TUNEL positive cells was similar between control diet and TLE fed IL-10−/−
mice (data not shown). In addition, TNF-induced apoptosis increased in IEC-18 cells exposed to TLE. These findings support the notion that TLE interferes with NF-κB-mediated pro-survival signals leading to increased apoptosis in the injured epithelium, thereby compromising barrier integrity. Since irradiation therapy, bacterial infection and non-steroidal anti-inflammatory drug exposure is associated with intestinal injury, a diet rich in lycopene could potentially interfere with repair mechanisms implicated in the restoration of the epithelium.