Nod2 Protects the Gut From Experimental Colitis Spreading to Small Intestine.

Background And Aims: Nucleotide oligomerization domain 2 [NOD2] mutations are key risk factors for Crohn's disease [CD]. NOD2 contributes to intestinal homeostasis by regulating innate and adaptive immunity together with intestinal epithelial function. However, the exact roles of NOD2 in CD and other NOD2-associated disorders remain poorly known.

Complementary Roles of Nod2 in Hematopoietic and Nonhematopoietic Cells in Preventing Gut Barrier Dysfunction Dependent on MLCK Activity.

Background: Crohn's disease (CD) pathogenesis is multifactorial involving genetic and environmental factors. Loss of function mutations in the nucleotide oligomerization domain 2 (NOD2) gene are the main genetic risk factor for CD. Like patients with CD, Nod2 mice are characterized by an enhanced Th1 immune response and a defective mucosal barrier function evidenced by increased intestinal permeability.

Nod2 Deficiency Leads to a Specific and Transmissible Mucosa-associated Microbial Dysbiosis Which Is Independent of the Mucosal Barrier Defect.

Background And Aims: Crohn's disease [CD] is a complex disorder characterised by an inappropriate immune response, impaired barrier function and microbial dysbiosis. Mutations in nucleotide oligomeriation domain 2 [NOD2] are CD risk factors. Increase of intestinal permeability, CD4 T cell infiltration, and bacterial dysbiosis are also seen in Nod2-knockout [Nod2 ] mice.

Respective Roles of Hematopoietic and Nonhematopoietic Nod2 on the Gut Microbiota and Mucosal Homeostasis.

Background: NOD2 mutations are associated with Crohn's disease (CD). Both CD (in human) and Nod2 deficiency (in mice) are characterized by increased mucosal CD4 T-cells, an altered permeability and a microbial dysbiosis. However, the respective roles of the gut epithelial and immune compartments on the phenotype are not known.

Pseudomonas fluorescens alters the intestinal barrier function by modulating IL-1β expression through hematopoietic NOD2 signaling.

Background: Ileal Crohn's disease is related to NOD2 mutations and to a gut barrier dysfunction. Pseudomonas fluorescens has also been associated with ileal Crohn's disease. The aim of this study was to determine the impact of P.

Yersinia pseudotuberculosis disrupts intestinal barrier integrity through hematopoietic TLR-2 signaling.

Intestinal barrier function requires intricate cooperation between intestinal epithelial cells and immune cells. Enteropathogens are able to invade the intestinal lymphoid tissue known as Peyer's patches (PPs) and disrupt the integrity of the intestinal barrier. However, the underlying molecular mechanisms of this process are poorly understood.

Yersinia pseudotuberculosis effector YopJ subverts the Nod2/RICK/TAK1 pathway and activates caspase-1 to induce intestinal barrier dysfunction.

Yersinia pseudotuberculosis is an enteropathogenic bacteria that disrupts the intestinal barrier and invades its host through gut-associated lymphoid tissue and Peyer's patches (PP). We show that the Y. pseudotuberculosis effector YopJ induces intestinal barrier dysfunction by subverting signaling of the innate immune receptor Nod2, a phenotype that can be reversed by pretreating with the Nod2 ligand muramyl-dipeptide.

Nod2 regulates the host response towards microflora by modulating T cell function and epithelial permeability in mouse Peyer's patches.

Nucleotide oligomerisation domain 2 (NOD2) mutations are associated with susceptibility to Crohn's disease and graft-versus-host disease, two human disorders related with dysfunctions of Peyer's patches (PPs). In Nod2(-/-) mice transcellular permeability and bacterial translocation are increased in PPs. In this study, we show that both anti-CD4(+) and anti-interferon gamma (anti-IFNgamma) monoclonal antibodies abrogate this phenotype and reduce the expression of tumour necrosis factor (TNF) receptor 2 and the long isoform of myosin light chain kinase, thus demonstrating that immune T cells influence the epithelial functions.

Nod2 mediates susceptibility to Yersinia pseudotuberculosis in mice.

Nucleotide oligomerisation domain 2 (NOD2) is a component of the innate immunity known to be involved in the homeostasis of Peyer patches (PPs) in mice. However, little is known about its role during gut infection in vivo. Yersinia pseudotuberculosis is an enteropathogen causing gastroenteritis, adenolymphitis and septicaemia which is able to invade its host through PPs.

CARD15/NOD2 is required for Peyer's patches homeostasis in mice.

Background: CARD15/NOD2 mutations are associated with susceptibility to Crohn's Disease (CD) and Graft Versus Host Disease (GVHD). CD and GVHD are suspected to be related with the dysfunction of Peyer's patches (PP) and isolated lymphoid follicles (LFs). Using a new mouse model invalidated for Card15/Nod2 (KO), we thus analysed the impact of the gene in these lymphoid formations together with the development of experimental colitis.

Improved tumor selectivity of radiolabeled peptides by receptor and antigen dual targeting in the neurotensin receptor model.

Radiolabeled peptides are emerging tools for diagnosis and therapy of tumors overexpressing receptors. However, binding to receptors expressed by nontumor tissues may cause toxicity. The objective of this study was to specifically enhance the binding affinity of labeled peptides to tumor cells, as opposed to receptor-positive nontumor cells, to ensure targeting selectivity.

Enhanced targeting specificity to tumor cells by simultaneous recognition of two antigens.

Radioimmunotherapy recently afforded convincing results for B-cell non-Hodgkin's lymphoma treatment with antibody specific for B-cell differentiation antigens. High doses of unlabeled or labeled antibodies are necessary to saturate specific sites on normal B-cells. We thus developed a new targeting strategy, taking advantage of dual binding cooperativity, to enhance the specificity of the radioactive uptake by tumor cells.

Steroid Regulation of Vasoactive Intestinal Peptide (VIP).

The present review is dedicated to the work of B.S. Mc Ewen on the regulatory effects of steroid hormones on peptidergic neurotransmission in the brain and pituitary.

Estradiol induces vasoactive intestinal peptide and prolactin gene expression in the rat anterior pituitary independently of plasma prolactin levels.

It is well established that estrogens are potent stimulators of prolactin (PRL) secretion. It has also been demonstrated that estradiol (E2) can increase the expression and the anterior pituitary levels of the vasoactive intestinal peptide (VIP), a peptide which also acts as a potent PRL-releasing factor. It thus remained unknown whether the effects on pituitary VIP were due to E2 itself or to E2-induced hyperprolactinemia (HPRL).

Coexpression of alpha and gamma enolase genes in neurons of adult rat brain.

Enolase (EC 4.2.1.

Adrenalectomy decreases vasoactive intestinal peptide mRNA levels in the rat suprachiasmatic nucleus.

Vasoactive intestinal peptide (VIP) concentrations were shown to be regulated by adrenal steroids. Therefore, we investigated whether adrenal steroids affect VIP mRNA levels, which would suggest an effect on VIP mRNA expression. Adrenalectomy performed on adult male rats resulted in a significant decrease in VIP mRNA in the hypothalamus (from 10.

Vasoactive intestinal peptide/peptide histidine isoleucine mRNA in the eye and suprachiasmatic nucleus of normal and monocularly enucleated rats.

The localization of the messenger RNA (mRNA) encoding vasoactive intestinal peptide/peptide histidine isoleucine (VIP/PHI) in the rat eye was studied by in situ hybridization histochemistry using a synthetic 35S-labeled oligodeoxyribonucleotide. Among the layers of the retina, specific labeling was found in the soma of some cells in the innermost lamina of the inner nuclear layer. Occasionally, labeled cells were also present in the ganglion cell layer.

Physiological roles of dopamine and neuropeptides in the retina.

The retina is a highly complex nervous tissue that converts light into patterns of electrical action potentials in order to process visual information. To carry out its function as a transducer and processor of visual information, the retina must be structurally and biochemically organized to send a coherent signal to the visual areas of the brain. In recent years, a number of biologically active substances have been demonstrated to be located within neurons in the retina.

Distribution of cells expressing vasoactive intestinal peptide/peptide histidine isoleucine-amide precursor messenger RNA in the rat brain.

The distribution of cells expressing vasoactive intestinal peptide/peptide histidine isoleucine-amide precursor messenger RNA was investigated in the rat brain and pituitary by in situ hybridization using a synthetic 35S-labeled oligonucleotide probe. Detection of labeled neurons by light-microscopic radioautography revealed a selective repartition of the messenger RNA-expressing cells. Several major vasoactive intestinal peptide/peptide histidine isoleucine-amide messenger RNA-containing cell groups were demonstrated including layers II-VI of the cerebral cortex, the suprachiasmatic nucleus and various thalamic structures such as the ventrolateral, posterior, lateral reticular, paracentralis and gelatinosus nuclei.

Autoradiographic characterization and localization of vasoactive intestinal peptide binding sites in albino rat and rabbit eyes.

Localization and pharmacological properties of vasoactive intestinal peptide (VIP) binding sites were investigated in eyes from albino rabbits and rats using an in vitro autoradiographic method. [125I]VIP was used as ligand, and various unlabelled peptides were studied to test the specificity of binding. Autoradiograms were generated by apposing 20-microns-thick cryostat eye sections to [3H]Hyperfilm or autoradiographic emulsion and quantified by means of image analysis procedures.

Estrogen-like effects of 7,12-dimethylbenz(a)anthracene on the female rat hypothalamo-pituitary axis.

We have recently demonstrated that 7,12-dimethylbenz(a)anthracene (DMBA), a potent inducer of mammary tumors in rodents, can in vitro decrease the number of membrane dopamine D2 receptors and stimulate prolactin (PRL) release, by direct estrogen-like actions on anterior pituitary. In the present study, we tested the ability of DMBA to mimic the in vivo estradiol (17 beta E2) effects on pituitary D2 receptors and on PRL as well as LH release. We have found that DMBA, like 17 beta E2, when injected to ovariectomized rats, induced a decrease in the number of anterior pituitary D2 receptors, a release of PRL and exerted a biphasic (acute negative and longer term positive) action on LH secretion.

[Autoradiographic localization and characterization of the ocular binding sites of the VIP (vasoactive intestinal peptide) in albino rats and rabbits].

Despite its name, Vasoactive Intestinal Peptide (VIP), a 28-amino acid peptide, is widely distributed in the eye where it is thought to play a physiological role, particularly in aqueous humor dynamics or retinal neurotransmission. Localization and pharmacological properties of VIP binding sites were investigated in eyes from albino rabbit and rat using an in vitro autoradiographic method. 125I-VIP was used as ligand and unlabelled VIP was used to displace labelled VIP.

Characterization and distribution of receptors for gonadotropin-releasing hormone in the rat hippocampus.

Distribution and properties of receptors for gonadotropin-releasing hormone (GnRH) were analyzed in the brain of adult male rats. Binding of the iodinated GnRH agonist Des-Gly10-(D-Ala6)-GnRH ethylamide was studied in hippocampus and anterior pituitary using three convergent approaches: quantitative autoradiography on frozen tissue, binding to fresh slices, and binding to crude membrane preparations. In all cases, binding was specific, saturable, and time, pH, and temperature dependent.

Autoradiographic localization of glucocorticosteroid binding sites in rat brain after in vivo injection of [3H]RU 28362.

The autoradiographic distribution of glucocorticosteroid binding sites in the brain of adrenalectomized rats was studied following in vivo injection of a potent synthetic glucocorticosteroid agonist [3H]RU 28362. Analysis of the autoradiograms revealed a specific and dense labeling in the pyramidal cell layer of the Ammon's horn and in the granular cell layer of the dentate gyrus of the hippocampus. In the hypothalamus, the labeling was particularly high in the paraventricular nucleus (site of CRF synthesis), the arcuate, periventricular and the supraoptic nuclei as well as in the median eminence.