1 Interleukin-12 (IL-12) plays a central role in the immune system by driving the immune response towards T helper 1 (Th1) type responses which are characterized by high IFN-g and low IL-4 production. In this study we investigated the eects of curcumin, a natural product of plants obtained from Curcuma longa (turmeric), on IL-12 production by mouse splenic macrophages and the subsequent ability of these cells to regulate cytokine production by CD4 + T cells. 2 Pretreatment with curcumin signi®cantly inhibited IL-12 production by macrophages stimulated with either lipopolysaccharide (LPS) or head-killed Listeria monocytogenes (HKL). 3 Curcumin-pretreated macrophages reduced their ability to induce IFN-g and increased the ability to induce IL-4 in Ag-primed CD4 + T cells. Addition of recombinant IL-12 to cultures of curcuminpretreated macrophages and CD4 + T cells restored IFN-g production in CD4 + T cells. 4 The in vivo administration of curcumin resulted in the inhibition of IL-12 production by macrophages stimulated in vitro with either LPS or HKL, leading to the inhibition of Th1 cytokine pro®le (decreased IFN-g and increased IL-4 production) in CD4 + T cells. 5 These ®ndings suggest that curcumin may inhibit Th1 cytokine pro®le in CD4 + T cells by suppressing IL-12 production in macrophages, and points to a possible therapeutic use of curcumin in the Th1-mediated immune diseases.

Background/AimsIschemic colitis (IC) is usually a self-limiting disease. But, it can cause necrosis that requires urgent surgical treatment. We sought to evaluate clinical difference in IC patients between medical and surgical treatment groups, and to identify prognostic factors for adverse outcomes.MethodsWe conducted a retrospective analysis of clinical characteristics in patients with IC treated in Chonnam National University Hospital between May 2001 and April 2010. A total of 81 patients with IC were enrolled. We classified the patients into two groups-a medical treatment group and a surgical treatment group-and evaluated their clinical features, treatment outcomes and mortality.ResultsAbsence of hematochezia, vomiting, abdominal tenderness, abdominal rebound tenderness, heart rate over 90 beats/min, systolic blood pressure less than 100 mm Hg, hyponatremia and increased LDH or serum creatinine level were observed more frequently in surgically-treated patients (p<0.05). Most cases in the medically-treated group resolved without complications (98.3%). But, about half of the cases (52.4%) of the surgically-treated group resolved and the mortality rate was 47.6%.ConclusionsIn patients with ischemic colitis, several clinical factors are associated with surgical treatment. Although IC is often selflimited, our data suggests that special attention and aggressive therapy is warranted in treating these patients.

The recepteur d'origine nantais (RON) receptor tyrosine kinase is overexpressed in epithelial cancers, including gastric cancer. The aims of the present study were to evaluate whether RON affects tumor cell behaviors and oncogenic signaling pathways, and to document the relationship of its expression with various clinicopathological parameters in gastric cancer. The biological role of RON in tumor cell behaviors and oncogenic signaling pathways was investigated by using small interfering RNA in gastric cancer cell lines including AGS and MKN28. The expression of RON in gastric cancer tissues was investigated by using reverse transcription polymerase chain reaction and immunohistochemistry. Knockdown of RON suppressed tumor cell migration and invasion in AGS and MKN28, induced apoptosis through modulation of anti-apoptotic and pre-apoptotic genes and induced cell cycle arrest by decreasing cyclin D1, cyclin D3 and CDK4, and by inducing p21 and p27 expression. Signaling cascades, including Akt and mitogen-activated protein kinase (MAPK), were significantly blocked by knockdown of RON. Expression of RON was significantly associated with tumor size, depth of invasion, lymph node metastasis, tumor stage and poor survival. These results indicate that RON is associated with tumor progression via the inhibition of apoptosis and cell cycle arrest in human gastric cancer.

These results indicate that black tea polyphenol theaflavin suppresses LPS-induced ICAM-1 and VCAM-1 expressions through blockage of NF-κB and JNK activation in intestinal epithelial cells.

KAI1 COOH-terminal interacting tetraspanin (KITENIN) contributes to tumor invasion and metastasis in various cancers. The aim of current study was to evaluate whether KITENIN affects tumor cell invasion and prognosis in human colorectal cancers. We investigated the biologic role of KITENIN on tumor cell invasion by using small interfering RNA in Caco2, DLD1, and SW480. We evaluated the expression of KITENIN and activator protein-1 (AP-1) target genes in human colorectal cancer tissues. The tumor cell invasion was decreased by knockdown of KITENIN in three tested cell lines. The mRNA expression of cyclin D1 and COX-2 was decreased in KITENIN knockdown Caco2 and the mRNA expression of MMP-3 and COX-2 was decreased in KITENIN knockdown DLD1 and SW480. The extracellular-signal protein kinase 1/2 (ERK1/2) phosphorylation was decreased in KITENIN knockdown in three tested cell lines. Expression of KITENIN and AP-1 target genes was significantly increased in human colorectal cancer tissues. The ERK1/2, c-Jun N-terminal kinase (JNK) and p38 phosphorylations were increased in human colorectal cancer tissues. Expression of KITENIN was significantly associated with lymphovascular invasion, depth of invasion, lymph node metastasis, tumor stage and poor survival. These results indicate that KITENIN is associated with human colorectal cancer progression including invasion and metastasis.

BackgroundBlack tea has been shown to elicit anti-oxidant, anti-carcinogenic, anti-inflammatory and anti-mutagenic properties. In this study, we investigated the impact of black tea extract (BTE) on lipopolysaccharide (LPS)-induced NF-κB signaling in bone marrow derived-macrophages (BMM) and determined the therapeutic efficacy of this extract on colon inflammation.MethodsThe effect of BTE on LPS-induced NF-κB signaling and pro-inflammatory gene expression was evaluated by RT-PCR, Western blotting, immunofluorescence and electrophoretic mobility shift assay (EMSA). The in vivo efficacy of BTE was assessed in mice with 3% dextran sulfate sodium (DSS)-induced colitis. The severity of colitis was measured by weight loss, colon length and histologic scores.ResultsLPS-induced IL-12p40, IL-23p19, IL-6 and IL-1β mRNA expressions were inhibited by BTE. LPS-induced IκBα phosphorylation/degradation and nuclear translocation of NF-κB/p65 were blocked by BTE. BTE treatment blocked LPS-induced DNA-binding activity of NF-κB. BTE-fed, DSS-exposed mice showed the less weight loss, longer colon length and lower histologic score compared to control diet-fed, DSS-exposed mice. DSS-induced IκBα phosphorylation/degradation and phosphorylation of NF-κB/p65 were blocked by BTE. An increase of cleaved caspase-3 and poly (ADP-ribose) polymerase (PARP) in DSS-exposed mice was blocked by BTE.ConclusionsThese results indicate that BTE attenuates colon inflammation through the blockage of NF-κB signaling and apoptosis in DSS-induced experimental colitis model.

These results indicate that knockdown of RON inhibits AP-1 activity and induces apoptosis and cell cycle arrest through the modulation of Akt/FoxO signaling in human colorectal cancer cells.

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