Endoplasmic reticulum stress (ER stress) in intestinal epithelial cells (IECs) plays an important role in the pathogenesis and perpetuation of inflammatory bowel disease (IBD). The aim of this study is to explore the potential of berberine (BBR) in regulating pro-inflammatory cytokine-induced ER stress and apoptosis in IECs. ER stress in cultured Caco-2 cells was induced by IFN-γ/TNF-α and tunicamycin, respectively. The experimental groups were pretreated with BBR. Cell viability was determined by MTT assay. In vitro apoptosis was examined by flow cytometry using annexin V-FITC labeling. The molecular markers of ER stress, including GRP-78, p-JNK, caspase-12, and cleaved caspase-3 were analyzed by Western blot. Xbp-1 mRNA splicing was detected by RT-PCR. Pretreatment of BBR helped to survive in cytokine-induced Caco-2 cells. BBR significantly attenuated cytokine-induced Caco-2 apoptosis. GRP78 expression and xbp-1 mRNA splicing were enhanced significantly in the presence of IFN-γ/TNF-α and tunicamycin, and they could be dampened by BBR. Further study revealed BBR could downregulate JNK phosphorylation, and the level of caspase-12 and cleaved caspase-3. Berberine can ameliorate pro-inflammatory cytokines induced ER stress in vitro, and it might be one of the targeted therapeutic agents for IBD.
RRH may be a reliable technique for treating early cervical cancer. Available evidence suggests that it is better than LRH for postoperative recovery, while the two techniques involve similar surgical outcomes and share the same limits in clinical practice.
Alemtuzumab, a humanized CD52 monoclonal antibody (mAb), has been used for immune induction in clinical small bowel transplantation (SBT). However, the local impact of CD52 mAb on the transplanted intestine is not known. In this study, we investigated the effects of CD52 mAb on the intestinal intraepithelial lymphocytes (iIELs) in grafts using a murine orthotopic SBT model. The antimouse CD52 mAb was used as a surrogate antibody. Graft rejection was assessed by histopathologic analysis, iIELs were isolated for flow cytometric analysis, the mucosal keratinocyte growth factor (KGF) expression was evaluated by real-time polymerase chain reaction, and epithelial cell (EC) proliferation (percent bromodeoxyuridine incorporation) was measured by immunohistochemistry. No mice showed evidence of rejection. Seven days after SBT, when the CD52 mAb was used, the numbers of iIELs and both T-cell receptor (TCR) γδ and TCRαβ subpopulations were decreased, and the number of TCRγδ iIELs of donor origin was prominently reduced in the allografts. Furthermore, TCRγδ iIEL-derived KGF messenger RNA expression and EC proliferation decreased significantly after CD52 mAb application. These data demonstrate that the antimouse CD52 mAb could deplete iIELs in the transplanted intestine, especially the TCRγδ subset of donor origin. The reduction of TCRγδ iIELs accompanied the decrease in mucosal KGF expression and EC proliferation, which may slow down the epithelial turnover and retard the repair of the damaged epithelium.
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