Molecular signatures differentiate immune states in type 1 diabetic families.

Mechanisms associated with type 1 diabetes (T1D) development remain incompletely defined. Using a sensitive array-based bioassay where patient plasma is used to induce transcriptional responses in healthy leukocytes, we previously reported disease-specific, partially interleukin (IL)-1-dependent signatures associated with preonset and recent onset (RO) T1D relative to unrelated healthy control subjects (uHC). To better understand inherited susceptibility in T1D families, we conducted cross-sectional and longitudinal analyses of healthy autoantibody-negative (AA(-)) high HLA-risk siblings (HRS) (DR3 and/or DR4) and AA(-) low HLA-risk siblings (LRS) (non-DR3/non-DR4).

Phosphatidylethanolamine is externalized at the surface of microparticles.

Microparticles (MPs) are membrane-bound vesicles shed normally or as a result of various (pathological) stimuli. MPs contain a wealth of bio-active macromolecules. Aminophospholipid phosphatidylserine (PS) is present on the surface of many MPs.

Human in vitro suppression as screening tool for the recognition of an early state of immune imbalance.

Regulatory T cells (Tregs) are critical mediators of immune tolerance to self-antigens. In addition, they are crucial regulators of the immune response following an infection. Despite efforts to identify unique surface marker on Tregs, the only unique feature is their ability to suppress the proliferation and function of effector T cells.

Anti-proliferative effect of a putative endocannabinoid, 2-arachidonylglyceryl ether in prostate carcinoma cells.

Endocannabinoids (ECs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG), inhibit proliferation of carcinoma cells. Several enzymes hydrolyze ECs to reduce endogenous EC concentrations and produce eicosanoids that promote cell growth. In this study, we determined the effects of EC hydrolysis inhibitors and a putative EC, 2-arachidonylglyceryl ether (noladin ether, NE) on proliferation of prostate carcinoma (PC-3, DU-145, and LNCaP) cells.

The type of responder T-cell has a significant impact in a human in vitro suppression assay.

Background: In type 1 diabetes (T1D), a prototypic autoimmune disease, effector T cells destroy beta cells. Normally, CD4(+)CD25(+high), or natural regulatory T cells (Tregs), counter this assault. In autoimmunity, the failure to suppress CD4(+)CD25(low) T cells is important for disease development.

Growth suppression of mouse pituitary corticotroph tumor AtT20 cells by curcumin: a model for treating Cushing's disease.

Background: Pituitary corticotroph tumors secrete excess adrenocorticotrophic hormone (ACTH) resulting in Cushing's disease (CD). Standard treatment includes surgery and, if not successful, radiotherapy, both of which have undesirable side effects and frequent recurrence of the tumor. Pharmacotherapy using PPARgamma agonists, dopamine receptor agonists, retinoic acid or somatostatin analogs is still experimental.

Curcumin (diferuloylmethane) induces apoptosis and blocks migration of human medulloblastoma cells.

Medulloblastoma (MB) is the most common malignant brain tumor in children. Bcl-2 and MMP-9 promote the pathogenesis and progression of MB. The expression of both bcl-2 and MMP-9 is regulated by the transcription factor NF-kappaB.

Curcumin (diferuloylmethane) inhibits cell proliferation, induces apoptosis, and decreases hormone levels and secretion in pituitary tumor cells.

Prolactinomas are the most prevalent functional pituitary adenomas. Dopamine D2 receptor (D2R) agonists, such as bromocriptine are the first line of therapy; however, drug intolerance/resistance to D2R agonists exists. Apart from D2R agonists, there is no established medical therapy for prolactinomas; therefore, identifying novel therapeutics is warranted.

Development of gallium compounds for treatment of lymphoma: gallium maltolate, a novel hydroxypyrone gallium compound, induces apoptosis and circumvents lymphoma cell resistance to gallium nitrate.

Clinical studies have shown gallium nitrate to have significant antitumor activity against non-Hodgkin's lymphoma and bladder cancer, thus indicating that gallium-based drugs have potential for further development as antineoplastic agents. In this study, we compared the cytotoxicity of gallium maltolate, a novel gallium compound, with gallium nitrate in lymphoma cell lines, including p53 variant and unique gallium nitrate-resistant cells. We found that gallium maltolate inhibited cell proliferation and induced apoptosis through the mitochondrial pathway at lower concentrations and more rapidly than gallium nitrate.

At-risk and recent-onset type 1 diabetic subjects have increased apoptosis in the CD4+CD25+ T-cell fraction.

Background: In experimental models, Type 1 diabetes T1D can be prevented by adoptive transfer of CD4+CD25+ (FoxP3+) suppressor or regulatory T cells. Recent studies have found a suppression defect of CD4+CD25+(high) T cells in human disease. In this study we measure apoptosis of CD4+CD25+(high) T cells to see if it could contribute to reduced suppressive activity of these cells.

Evidence of a functional role for mast cells in the development of type 1 diabetes mellitus in the BioBreeding rat.

Human type 1 diabetes mellitus (T1DM) arises through autoimmune destruction of pancreatic beta cells and is modeled in many respects by the lymphopenic and spontaneously diabetic BioBreeding (BB) DRlyp/lyp rat. Previously, preonset expression profiling of whole DRlyp/lyp pancreatic lymph nodes (PLN) revealed innate immune activity, specifically that of mast cells and eosinophils. Furthermore, we observed that pancreatic islets of DRlyp/lyp rats as well as those of diabetes-inducible BB DR(+/+) rats potentially recruit innate cells through eotaxin expression.

Characterization of CD 200-receptor expression in the murine epidermis.

CD 200 is a widely expressed transmembrane glycoprotein that transmits an inhibitory signal after ligation of the structurally homologous CD 200-receptor-1 (CD 200 R1). Recently, we showed that CD 200 is expressed on keratinocytes and plays a role in protecting hair follicles from autoimmune attack. Here, we report the characterization of cell surface and mRNA expression of CD 200 R1 by cells of the murine epidermis.

Expression of CD200 on epithelial cells of the murine hair follicle: a role in tissue-specific immune tolerance?

CD200 (OX-2) is a transmembrane glycoprotein that transmits an immunoregulatory signal through the CD200 receptor (CD200R) to attenuate inflammatory reactions and promote immune tolerance. CD200 expression in the skin has not been described previously. We now report that freshly isolated cells of the murine epidermis contain a subpopulation of major histocompatibility complex (MHC) class II-negative, CD3-negative keratinocytes that are CD200-positive.

The T cell activation marker CD150 can be used to identify alloantigen-activated CD4(+)25+ regulatory T cells.

We have been investigating whether alloantigen-specific CD4(+)25+ regulatory T cells can be identified for use in treating graft-versus-host disease. CD150, which is upregulated on the surface of all activated T lymphocytes, was identified as a candidate marker for alloantigen-activated CD4(+)25+ regulatory T cells by gene chip analysis. Freshly isolated CD4(+)25+ cells had only low cell-surface expression of CD150, comparable to that of CD4(+)25- T cells.

Immunomodulation in stable renal transplant recipients with concomitant tacrolimus and sirolimus therapy.

BACKGROUND: Long term treatment with immunosuppressive agents results in nephrotoxicity in renal transplant recipients. We explored the effect of combination of Tacrolimus (TAC) and Sirolimus (SRL) on the immune system in renal transplant recipients. METHODS: 10 stable renal transplant recipients were selected to participate in a pharmacokinetic study with a combination of TAC and SRL.