An ancestral retroviral protein identified as a therapeutic target in type-1 diabetes.

Human endogenous retroviruses (HERVs), remnants of ancestral viral genomic insertions, are known to represent 8% of the human genome and are associated with several pathologies. In particular, the envelope protein of HERV-W family (HERV-W-Env) has been involved in multiple sclerosis pathogenesis. Investigations to detect HERV-W-Env in a few other autoimmune diseases were negative, except in type-1 diabetes (T1D).

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.

Transplantation tolerance induced in humans at the fetal or the neonatal stage.

Patients transplanted with HLA-mismatched stem cells from fetal livers develop transplantation tolerance to donor antigens. Engraftment needs no conditioning regimen prior to transplantation in neonates with severe combined immunodeficiency disease or in human fetal patients having not yet developed any immune maturity, especially T-cell differentiation. The chimeric patients have donor-derived T lymphocytes which progressively demonstrate positive interactions with other host cells.

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.

HIV-1 infection: functional competition between gp41 and interleukin-2.

To determine whether the gp41 of HIV-1 could adhere to the interleukin (IL)-2 receptor at the surface of target cells in vitro, we analysed in vitro the possible functional competition between various forms of the HIV-1 gp41 molecule (i.e. peptides, trimeric or primary structures) and IL-2.

Preferential increase in memory and regulatory subsets during T-lymphocyte immune reconstitution after Thymoglobulin induction therapy with maintenance sirolimus vs cyclosporine.

Background: Sirolimus maintenance therapy with Thymoglobulin induction is a promising regimen that may preserve renal function. Data are lacking, however, about the immunologic effects of combined Thymoglobulin-sirolimus.

Methods: In a 12-month, prospective, randomised, open-label, single-centre pilot study, de novo deceased-donor kidney transplant patients were randomised to receive cyclosporine or sirolimus, with Thymoglobulin induction, mycophenolate mofetil and corticosteroids.

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.

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.

Different mechanisms are involved in apoptosis induced by melanoma gangliosides on human monocyte-derived dendritic cells.

Tumor escape is linked to multiple mechanisms, notably the liberation, by tumor cells, of soluble factors that inhibit the function of dendritic cells (DC). We have shown that melanoma gangliosides impair DC differentiation and induce their apoptosis. The present study was aimed to give insight into the mechanisms involved.

Immunosuppressive networks in the tumour environment and their effect in dendritic cells.

The failure of the immune system to provide protection against tumour cells is an important immunological problem. It is now evident that inadequate function of the host immune system is one of the main mechanisms by which tumours escape from immune control, as well as an important factor that limits the success of cancer immunotherapy. In recent years, it has become increasingly clear that defects in dendritic cells have a crucial role in non-responsiveness to tumours.

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.

Dendritic cells dysfunction in tumour environment.

Several studies indicate that most tumours are immunogenic and they rarely succeed to induce an efficient immune response. Many mechanisms have been involved in the tumour escape from host immune surveillance. The tumour microenvironment has emerged as an important component contributing to dendritic cells (DCs) dysfunction.

[Infectious complications due to immunosuppression in organ transplant patients].

Prevention and treatment of allograft rejection by immunosuppressive treatments expose organ transplant patients to frequent and sometimes severe infectious complications. Immunosuppressive drugs inhibit both the immune response to alloantigens, and the anti-infectious immunity; they promote intracellular infections, including infections with viruses and with bacterial, parasitic and mycotic agents. Infectious risks are related to duration of immunosuppression exposure, type of immunosuppressive drugs, combination of drugs and trough levels required to control rejection.