BACKGROUND Curcumin, the yellow pigment in turmeric, has been shown to prevent tumor progression in a variety of tissues in rodents. The authors investigated the effect of curcumin on human carcinoma cell lines to determine whether constitutive interleukin‐8 (IL‐8) production of tumor cells was correlated with nuclear factor κB (NF‐κB) activation and cell growth activity. METHODS A human pancreatic carcinoma cell line, SUIT‐2, was incubated with various concentrations of curcumin for 2 hours. Biologic features, including IL‐8 production, DNA binding activity, transactivation of NF‐κB, cell growth activity, cell viability, and the expression of IL‐8 receptors (CXCR1 and CXCR2) were analyzed. RESULTS The constitutive production of IL‐8 was inhibited by curcumin at concentrations of 10–100 μM in a dose dependent manner. NF‐κB activity was reduced significantly by curcumin treatment. Pretreatment with curcumin inhibited the growth rate of carcinoma cells significantly. Such cell growth inhibition by curcumin was not recovered by exogenous recombinant IL‐8. The investigation of expression in IL‐8 receptors, CXCR1 and CXCR2, revealed that the expression of both receptors was enhanced remarkably by curcumin. Exogenous IL‐8 could not recover this enhancement of IL‐8 receptors. These results suggest that curcumin inhibits IL‐8‐induced receptor internalization. CONCLUSIONS The authors concluded that curcumin contributed not only to the inhibition of IL‐8 production but also to signal transduction through IL‐8 receptors. These data suggest that curcumin reduces numerous IL‐8 bioactivities that contribute to tumor growth and carcinoma cell viability. From this point of view, curcumin is a potent anticancer agent that inhibits the production of proinflammatory cytokines, including IL‐8, by tumor cells. Cancer 2002;95:1206–14. © 2002 American Cancer Society. DOI 10.1002/cncr.10812

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Neutrophil elastase, which enhances intercellular adhesion molecule-1 (ICAM-1) expression in endothelial cells, plays an important role in ischemia/reperfusion injury. Here, we investigated signal transduction of ICAM-1 expression in endothelial cells stimulated by neutrophil elastase. Pretreatment of animals with the neutrophil elastase inhibitor, ONO-5046.Na significantly decreased the number of neutrophils or Mac-1(+) (CD11b/CD18) cells in ischemic liver lobes after reperfusion. ICAM-1 expression in the rat endothelial cell line (WK-5) was significantly upregulated after stimulation with neutrophil elastase, but this reaction was inhibited by the neutrophil elastase inhibitor ONO-5046.Na. ICAM-1 mRNA expression, which is induced by neutrophil elastase in a dose-dependent manner, was repressed by the alpha1-protease inhibitor. ICAM-1 expression, stimulated by neutrophil elastase, was partially reduced by a diacylglycerol kinase inhibitor and protein kinase C inhibitor, but was completely inhibited by a phospholipase C inhibitor, cytosolic Ca(2+) chelator, calmodulin antagonist, and nuclear transcription factor kappa B inhibitor. Binding of (125)I-neutrophil elastase to WK-5 cells was competitively inhibited by the addition of unlabeled neutrophil elastase. The neutrophil elastase inhibitor significantly reduces ICAM-1 expression and Mac-1(+) cell accumulation in ischemic liver lobes after reperfusion. Neutrophil elastase stimulates ICAM-1 expression in endothelial cells by intracellular signal transduction via activation of diacylglycerol kinase, protein kinase C, phospholipase C, Ca(2+)-calmodulin, and nuclear transcription factor kappa B.

Little is known regarding the role of ␥␦ ؉ T cells in organ transplantation. We previously reported that immunologic unresponsiveness is induced by prior donor-specific blood transfusion (DST) in rat hepatic allografts. We investigated the phenotype and distribution of ␥␦ ؉ T cells in the hepatic allograft, spleen, and peripheral blood of recipient rats with immunologic unresponsiveness induced by DST. ␥␦ ؉ T cells were enumerated in allograft livers and spleens by immunostaining and in blood by flow cytometric analysis. The phenotype of ␥␦ ؉ T cells was determined using CD45RC isoforms derived from alternative mRNA splicing. The great majority of mature human T lymphocytes express the ␣␤ T-cell receptor (TCR). A small population, which represents 0.5% to 16% of T lymphocytes in peripheral blood and lymphoid tissues, express the ␥␦ TCR. 1 Despite the fact that ␥␦ ϩ T cells are mature lymphocytes and have several phenotypic similarities to ␣␤ ϩ T cells, the biologic role of this cell population is still poorly understood. 2 ␥␦ ϩ T cells recognize class I and class II major histocompatibility complex (MHC) antigens. 3,4 However, non-MHC restricted cytotoxicity of ␥␦ ϩ T cells has been reported. 5 Thus, the preferential ligands for ␥␦ ϩ T cells have not yet been identified.Alloreactive ␥␦ ϩ T cells can trigger a rejection response, 6 and in fact, ␥␦ ϩ T cells are known to be involved in human renal allograft rejection 7 and in graft vascular disease. 8 However, ␥␦ ϩ T cells also may participate in cardiac allograft tolerance. 9,10 ␥␦ ϩ T cells from mice or rats selectively depleted of ␣␤ T cells seem to be unable to mount an alloreactive response, 11 but the role of ␥␦ ϩ T cells in organ transplantation is not clear.Leukocyte common antigen (LCA), CD45, has many isoforms derived from alternative mRNA splicing. 12 Six different CD45 isoforms have been identified from cDNA clones (usage of ABC, AB, BC, B, C, and O exons), and another is inferred (A exon alone) from hybridization studies. 13 Yang et al., 14 demonstrated functional maturation of recent thymic emigrants in the periphery, showing that the development of alloreactivity correlates with cyclic expression of CD45RC isoforms. LCA isoforms are associated with functional T-cell subsets including memory, activated, and alloreactive T cells. 15 In the rat, ␥␦ ϩ T-cell subsets are distinguished by membrane expression of the high (CD45RC ϩ ) and low (CD45RC Ϫ ) molecular weight isoforms of CD45. 16 We previously showed that persistent infiltration of CD45RC Ϫ CD4 ϩ T cells, Th2-like effector cells, was associated with immunologic unresponsiveness in rat hepatic allografts when animals were pretreated with donor-specific transfusion (DST) before transplantation. 17 However, little is known about the phenotype of ␥␦ ϩ T cells based on CD45RC expression in transplant immunology. The present study was undertaken to investigate the phenotype and distribution of ␥␦ ϩ T cells in rat hepatic allografts during acute rejection and their possible role in immunologic unrespons...