Prope tolerance to heart allografts in mice associated with persistence of donor interleukin-10-transduced stem cells.

Background: We previously reported that transduction of the human interleukin (IL)-10 gene into the total fetal liver stem cells (hIL-10-TFLs) of mice protects against their rejection in an allogeneic host. In this study, we explored the effects of these cells in two different models of organ transplantation.

Methods: Balb/c mice were sublethally irradiated before receiving skin or vascularized heterotopic heart grafts from C57Bl/6 mice.

Administration of the selective cyclooxygenase (COX)-2 inhibitor etodolac prolongs cardiac allograft survival in a mouse model.

Etodolac, a selective cyclooxygenase-2 (COX-2) inhibitor, is a non-steroidal anti-inflammatory drug. COX-2 is a key factor in the progression of inflammation. Although inflammation is an essential pathologic feature of cardiac allograft rejection, the role of COX-2 in this process remains unclear.

Expression of sphingosine-1 phosphate receptor in rat renal ischemia-reperfusion injury.

Sphingosine-1 phosphate receptor (S1PR) has come to the fore as a mediator of extracellular signaling through its interaction with G-protein-coupled receptors, which results in the induction of peripheral T-cell depletion. The mechanisms involved in renal ischemia-reperfusion (I/R) injury are complex, but appear to involve the early participation of bone marrow-derived cells, such as T lymphocytes. In this study, we investigated the expression of SIPR in a rat model of renal I/R injury.

Bromohydrin pyrophosphate-stimulated Vgamma9delta2 T cells expanded ex vivo from patients with poor-prognosis neuroblastoma lyse autologous primary tumor cells.

Gamma/delta T cells (Vgamma9delta2) contribute to innate immunity and exert natural cytotoxicity against a variety of tumors. Using a synthetic phosphoantigen (Bromohydrin Pyrophosphate, BrHPP), we amplified Vgamma9delta2 T cells in vitro from neuroblastoma patients. In the presence of BrHPP and low doses of IL-2, robust proliferation of Vgamma9delta2 T cells was obtained from peripheral blood mononuclear cells (PBMC) harvested at diagnosis.

Telmisartan inhibits human urological cancer cell growth through early apoptosis.

Angiotensin II receptor blockers (ARBs) are widely used as hypertensive therapeutic agents. In addition, studies have provided evidence that ARBs have the potential to inhibit the growth of several types of cancer cells. It was reported that telmisartan (a type of ARB) has peroxisome proliferator-activated receptor (PPAR)-γ activation activity.

The role of cysteinyl-LT(1)receptor (CysLT(1)R) in renal ischemia-reperfusion injury.

The pathogenesis of ischemia-reperfusion (I/R) injury is known to involve cytokines and particularly surface adhesion molecules, the expression of which initiates the attachment of inflammatory cells. Renal I/R injury, a clinically important problem, is an invariable consequence of renal transplantation. The problem begins at the onset of acute tubular necrosis (ATN), when the transplantation includes a long ischemic interval or by use of a cardiac arrest donor's kidney.

Telmisartan as a peroxisome proliferator-activated receptor-γ ligand is a new target in the treatment of human renal cell carcinoma.

Angiotensin II receptor blockers (ARBs) are widely used as hypertensive therapeutic agents. However, it has been reported that Telmisartan (a type of ARB) additionally activates peroxisome proliferator-activated receptor (PPAR)-γ. We previously reported that PPAR-γ ligand induced the growth arrest of renal cell carcinoma (RCC) cells through apoptosis, and that Telmisartan had the potential to inhibit prostate cancer cell growth through apoptosis.

Expression of cysteinylLT1 receptor in human testicular cancer and growth reduction by its antagonist through apoptosis.

The metabolism of arachidonic acid by either cyclooxygenase or lipoxygenase is believed to play an important role in carcinogenesis. Leukotriene (LT) D4 is a pro-inflammatory mediator derived from arachidonic acid through various enzymatic steps, and 5-lipoxygenase is an important factor in generating LTD4. We investigated LTD4 receptor (cysteinylLT1 receptor; CysLT1R) expression in testicular cancer (TC), as well as the effects of the CysLT1R antagonist on cell proliferation in a TC cell line.

Study of cysteinyl leukotriene-1 receptor in rat renal ischemia-reperfusion injury.

Renal ischemia-reperfusion (I/R) injury is a major cause of renal transplant dysfunction. Recent studies of I/R injury have focused on the function of neutrophils, the mechanisms of action of inflammatory cytokines, and oxygen free radicals, as well as other mediators. However, few reports address the cysteinyl leukotriene-1 receptor (CysLT1R), an important mediator of bronchial asthma in human beings.

Telmisartan is a potent target for prevention and treatment in human prostate cancer.

Angiotensin II receptor blockers (ARBs) are widely used as hypertensive therapeutic agent. Recent studies have reported that ARBs have the potential to inhibit the growth of prostate cancer (PC) cells. Moreover, it was recently reported that Telmisartan (a kind of ARB) has peroxisome proliferator-activated receptor (PPAR)-gamma activation.

Relationship between peroxisome proliferator-activated receptor-γ and renal ischemia-reperfusion injury.

The pathogenesis of ischemia-reperfusion (I/R) injury is known to involve cytokines and, in particular, surface adhesion molecules, the expression of which initiates inflammatory cell attachment. It has been suggested that peroxisome proliferator-activated receptor (PPAR)-γ is an important immunomodulatory factor as well as a regulator of fatty acid. In this study, we investigated the expression of PPAR-γ in a renal I/R injury rat model.

The role of arachidonic acid in a rat renal ischemia-reperfusion injury model.

The metabolism of arachidonic acid by either the cyclooxygenase (COX) or the lipoxygenase (LOX) pathway generates eicosanoids, which have been implicated in the pathogenesis of a variety of human diseases, including ischemia-reperfusion (I/R) injury. Several reports have demonstrated that COX-2 and LOX inhibitors can reduce the damage caused by I/R injury. However, few reports have investigated the effects of COX and LOX expression on renal I/R injury, thus this study aimed to do so in a rat renal I/R injury model.

The effect of neutrophil elastase inhibitor on acute tubular necrosis after renal ischemia-reperfusion injury.

In renal transplantation, ischemia-reperfusion (I/R) injury is a major cause of renal dysfunction. Activated neutrophils are reported to be closely involved in I/R injury after renal transplantation. Neutrophil elastase, a protease released from activated neutrophils, damages tubular endothelial cells.

Human interleukin-10 transduced fetal liver stem cells prolong survival of mouse skin and heart allografts.

Interleukin (IL)-10 regulates immune responses, acting as a suppressive cytokine by inhibiting the synthesis of Th1 cytokines, such as IL-2 and interferon (IFN)-gamma. It also strongly down-regulates major histocompatibility complex (MHC) class II determinants on antigen presenting cells (APC). On the other hand, long-term tolerance is well correlated with the persistence of a peripheral microchimerism.

Prolonged survival of mouse skin allografts after transplantation of fetal liver cells transduced with hIL-10 gene.

Introduction: Interleukin-10 (IL-10) is a cytokine with a moleculary weight of 18 kDa, that was first identified as being produced by Th2 cells. It appears to have anti-inflammatory action by diminishing the production of pro-inflammatory cytokines produced by Th1 cells. IL-10 also regulates the differentiation and proliferation of several immune cells such as T cells, B cells, natural killer cells, antigen-presenting cells, mast cells and granulocytes.

Increased frequency of CD3/8/56-positive umbilical cord blood T lymphocytes after allo-priming in vitro.

Umbilical cord blood (UCB) or adult peripheral blood mononuclear cells (PBMC) were repeatedly stimulated by HLA-mismatched allogeneic Epstein-Barr virus (EBV)-transformed cell lines, and the bulk responders or single-cloned cells were immunophenotypically analyzed by flow cytometry. One month after the allo-stimulation, not in PBMC but in UCB, the proportion of CD3/8/56 triple positive T lymphocytes significantly increased. Furthermore, UCB clones exhibited those unique CD3/8/56 markers at an extremely higher frequency than PB clones.

Expression of nonmuscle myosin heavy chain B (SMemb) in rat allogeneic kidney transplantation.

Background/aim: Investigators have reported that the nonmuscle myosin heavy chain B (SMemb) expression is enhanced in various types of glomerular diseases which develop into nephrosclerosis. In renal transplantation, transplant glomerulitis is often recognized during acute rejection. Therefore, we hypothesized that SMemb plays important roles in acute kidney rejection.

Hepatocyte growth factor (HGF) as a rapid diagnostic marker and its potential in the prevention of acute renal rejection.

Several investigators have reported that hepatocyte growth factor (HGF) may be related to the protection or reconstruction of the kidney during acute renal rejection. To address this question, we examined the relationship between HGF and acute rejection in the following two studies with rat renal transplantation models. In study 1, the relationship between serum HGF levels and acute renal rejection in iso-, allo- and allograft with cyclosporine (CsA)-treated models was examined.

Expression of cyclooxygenase-2 in patients with bladder carcinoma.

Purpose: Cyclooxygenase-2 is considered to have an important role in the development of metastasis in cancer due to angiogenesis function. The expression of cyclooxygenase-2 was found to be up-regulated in colorectal carcinoma and other cancers. We investigated cyclooxygenase-1 and 2 expressions in patients with bladder cancer, chronic cystitis and normal bladder.

The efficient generation of CD83 positive immunocompetent dendritic cells from CD14 positive acute myelomonocytic or monocytic leukemia cells in vitro.

The ability of leukemic cells to differentiate to mature dendritic cells (DCs) was investigated in six acute myelomonocytic or monocytic leukemia cases. It was found that CD14 positive cells were more efficiently changed to CD83 positive mature typed DCs with granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin-4 (IL-4) and tumor necrosis factor alpha (TNF-alpha) compared with CD14 negative cells. Such leukemia derived DCs expressed a sufficient level of costimulatory molecules (CD80 and CD86), and were shown to be monoclonal based on an the X-inactivation analysis.