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.

A 69-year-old male visited our medical center with hematemesis. Gastrofibroscopy revealed a 4.5 cm sized fungating mass on anterior wall of gastric lower body. Biopsy specimens showed a carcinoma of neuroendocrine components with strong positive for synaptophysin stain. Because he had a metastatic neuroendocrine carcinoma with multiple metastasis of liver, we treated him with chemotherapy of etoposide and cisplatin. The primary lesion showed nearly complete response after 6th cycles of chemotherapy, however it was regrowed with chemoresistance and mutifocal lesion in stomach and liver. Endoscopic biopsy on same previous lesion revealed a poorly differentiated tubular adenocarcinoma with negative for synaptophysin. After conversion to another tumor type, the treatment outcome was progressed in spite of salvage chemotherapy for gastric adenocarcinoma. He died 17 months after diagnosis. The immunohistological change of same mass after chemotherapy suggests a possibility of other course of differentiation from common pleuripotent cells of adenocarcinoma and neuroendocrine carcinoma after chemotherapy.

CD47 possesses a variety of anti-tumor, anti-angiogenic, and anti-metastatic properties in several tumors, but its roles on EBV-transformed B cells are still not fully understood. Here we first observed that EBV infection induced CD47 expression on B cells surface, and CD47 stimulation of EBV-transformed B cells with anti-CD47 mAb (B6H12) reduced cell proliferation and induced the cell cycle arrest at G1-phase. We showed that CD47-induced G1-phase arrest was mediated through increased expression of CDKi (p16INK4a, p21WAF1, and p53), a simultaneous decreased expression in CDK2, 4, 6 and cyclin D1, D2 and E and enhanced binding of CDKi-CDK. Among the relevant pathways, CD47 mAb induced outstanding activation of p38 MAPK and JNK, whereas phosphorylation of Akt and ERK1/2 were both reduced. In particular, p38 inhibitor SB203580 and JNK inhibitor SP600125 powerfully blocked the decreased expression of CDK and the increased expression of CDKi and dramatically suppressed binding of phospho-p38-CDKi. Accordingly, these data demonstrate that the p38 MAPK and JNK pathway participates in CDKi induction, subsequently leading to a decrease in the levels of cyclin D1-CDK4/6 and cyclin E-CDK2 complexes and CD47-dependent EBV-transformed B cell growth inhibition. In conclusion, these findings concerning the molecular mechanisms of CD47 signaling in EBV-transformed B cells provides a theoretical basis for clinical approaches for the use of therapeutic agents in treating EBV-associated tumors.

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