Inducible nitric oxide synthase expression in vascular and glomerular structures of human chronic allograft nephropathy.

Nitric oxide (NO) plays an important role in the cytotoxic mechanisms responsible for acute renal allograft rejection, where macrophages produce high levels of inducible nitric oxide synthase (iNOS). By contrast, both the source and the role of NO in chronic allograft nephropathy (CAN) are still unclear. In this study, the expression of iNOS mRNA and protein was assessed in the kidneys of patients with graft failure due to chronic rejection.

Assessment of chemokine receptor expression by human Th1 and Th2 cells in vitro and in vivo.

The preferential association of some chemokine receptors with human Th1 or Th2 cells has recently been reported. In this study, the expression of CCR3, CCR5, CXCR3, and CXCR4 were analyzed by flow cytometry in three distinct in vitro models of Th1/Th2 polarization, activated naive and memory T cells, and T-cell clones, in which the intracellular synthesis of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) and the surface expression of CD30 and LAG-3 were also assessed. Moreover, by using immunohistochemistry the in vivo expression of CCR3, CCR5, CXCR3, and CXCR4 was examined in the gut of patients suffering from Crohn's disease, a Th1-dominated disorder, and in the skin of patients suffering from systemic sclerosis, a Th2-dominated disorder.

Angiotensin II stimulates the synthesis and secretion of vascular permeability factor/vascular endothelial growth factor in human mesangial cells.

The aim of the present study was to evaluate the role of angiotensin II (AngII) in regulating both the gene expression and secretion of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) in human mesangial cells (HMC) in culture. Densitometric analysis of Northern blot experiments demonstrated that AngII increases VPF/VEGF mRNA in a dose-dependent manner. The levels of VPF/VEGF mRNA in HMC exposed for 3 h to 10 nM, 100 nM, and 1 microM AngII were, respectively, 1.

Molecules associated with human Th1 or Th2 cells.

In the last few years, some surface molecules which preferentially associate with human Th1 or Th2 cells have been described. Th1-related molecules include CD26, membrane IFN-gamma, LAG-3, CCR5 and CXCR3, whereas CD62L, CD30, CCR3, CCR4, CCR8, and in a certain way even CXCR4, preferentially associate with human Th2 cells during certain phases of their differentiation/activation process. Although none of these molecules can be considered as a truly selective marker of human Th1 or Th2 cells, their combined detection may help to characterize the pathway of the specific immune response both in vitro and in vivo.

Enhanced HIV expression during Th2-oriented responses explained by the opposite regulatory effect of IL-4 and IFN-gamma of fusin/CXCR4.

The human alpha-chemokine receptor fusin/CXCR4 is an important cofactor for entry of T lymphocyte-tropic HIV-1 strains. We investigated the possible regulatory role of T cell cytokine patterns on CXCR4 as well as HIV expression by using in vitro models of both secondary and primary immune responses. Antigen-specific memory CD4+ T cells infected with a T-tropic HIV-1 strain showed significantly higher CXCR4 and HIV-1 expression in Th0/2-oriented responses in comparison with Th1-oriented responses.

High CD30 ligand expression by epithelial cells and Hassal's corpuscles in the medulla of human thymus.

CD30 is a member of tumor necrosis factor (TNF) receptor superfamily that is expressed by activated T cells in the presence of interleukin-4 (IL-4). Although CD30 can mediate a variety of signals, CD30-deficient mice have impaired negative selection of T cells, suggesting that at least in the context of murine thymus, CD30 is a cell death-mediating molecule. The ligand for CD30 (CD30L) is a membrane-associated glycoprotein related to TNF, which is known to be expressed mainly by activated T cells and other leukocytes.

T cells and cytokines in Crohn's disease.

Recent findings indicate that activated T lymphocytes, showing restricted T-cell receptor repertoire and a Th1-like profile of cytokine production, are responsible for macrophage activation and release of inflammatory cytokines, toxic oxygen metabolites and nitric oxide, which initiate and maintain the transmural intestinal inflammation in Crohn's disease. A critical event in the promotion of Th1-type response at gut level may involve up-regulation of IL-12 production and the breakdown of tolerance against the intestinal flora.

Insulin-like growth factor binding protein production in bovine retinal endothelial cells.

Retinopathy is the most frequent microangiopathic complication in diabetes. Many circulating hormones and locally produced mitogenic factors have been involved. Bovine retinal endothelial cells (BRECs) were cultured to investigate if insulin, insulin-like growth factors (IGFs), IGF binding proteins (IGFBPs), and a chronic high-glucose condition could control endothelial cell growth.

Localization of endothelin-converting enzyme-1 in human kidney.

The distribution of endothelin-converting enzyme-1 (ECE-1) mRNA and protein was investigated in human kidney excised because of renal tumors. ECE-1 immunoreactivity was detected by immunohistochemistry throughout the different areas of the kidney in the vascular and tubular structures. In the cortex, ECE-1 immunostaining was present in the endothelial surface of arcuate and interlobular arteries and in arterioles.

Type 2 helper T-cell predominance and high CD30 expression in systemic sclerosis.

The pattern of cytokine production of skin-infiltrating T cells from patients with progressive systemic sclerosis was investigated. Most CD4+ T-cell clones generated from skin biopsy specimens showed a type 2 helper (Th2) cytokine profile (production of interleukin-4, but no interferon (IFN)-gamma). High interleukin-4 but little or no IFN-gamma mRNA expression was found by in situ hybridization in skin perivascular mononuclear cell infiltrates.

An update on human Th1 and Th2 cells.

The existence of functionally polarized human T cell responses based on their profile of cytokine secretion in both the CD4+ T helper (Th) and the CD8+ T cytotoxic cell subset has been established. Human Th1 and Th2 cells not only produce a different set of cytokines but also exhibit distinct functional properties and preferential expression of some activation markers, such as LAG-3 and CD30, respectively. Several factors are involved in the Th cell differentiation into the polarized Th1 or Th2 pathway.

In vivo CD30 expression in human diseases with predominant activation of Th2-like T cells.

CD30 is a member of the tumor necrosis factor (TNF) receptor family, originally described as a marker for Hodgkin and Reed-Sternberg cells in Hodgkin's disease, which has been found to be preferentially expressed by T cells producing Th2-type cytokines. The presence of CD30 expression was assessed by both immunohistochemistry and reverse transcriptase-polymerase chain reaction in the target organs of patients with Th1- or Th2-dominated disorders. CD30 expression was found in neither the gut of patients with Crohn's disease nor in the gastric antrum of Helicobacter pylori-infected patients, where there was high interferon-gamma (IFN-gamma) expression.

Type 1 T-helper cell predominance and interleukin-12 expression in the gut of patients with Crohn's disease.

Crohn's disease (CD) is a chronic bowel inflammatory disorder in which the pathogenic role of immune alterations has been suggested, but the immunologic mechanisms responsible for the inflammatory reaction are still poorly understood. We investigated the profile of cytokine secretion by T-cell clones generated from gut tissue specimens of four patients with active CD, five patients with ulcerative colitis, and four patients with noninflammatory gut disorders (NIGDs). The great majority of CD4+ T-cell clones generated from the gut of patients with CD produced high levels of interferon-gamma (IFN-gamma) but low or undetectable amounts of interleukin-4 (IL-4), whereas substantial proportions of CD4+ T-cell clones derived from the gut of patients with either ulcerative colitis or NIGDs produced IL-4 in addition to IFN-gamma.

Immune mechanisms in the pathogenesis of inflammatory gastrointestinal disorders.

The cytokine secretion profile of T cells present in the gastric antrum of Helicobacter pylori-infected patients with peptic ulcer and in the gut of patients with Crohn's disease was investigated. A type 1 T helper (Th1)-dominated response was detected in the gastric antrum of Helicobacter pylori-infected subjects with peptic ulcer by both reverse transcriptase-PCR and immunohistochemistry. By using a T-cell cloning technique, it was shown that the majority of Th 1 cells were specific for Hp antigens.