Role of endothelin-1 in the migration of human olfactory gonadotropin-releasing hormone-secreting neuroblasts

FNC-B4 neuroblasts that express both neuronal and olfactory markers have been established and cloned. These cells express GnRH and both the endothelin-1 (ET-1) gene and protein and respond in a migratory manner to GnRH in a dose-dependent manner. Previous research has shown that FNC-B4 cells produce and respond to ET-1 by regulating the secretion of GnRH through endothelin type A receptors and by stimulating their proliferation through endothelin type B (ETB) receptors. In this study, we found that FNC-B4 cells are able to migrate in response to ET-1 through the involvement of ETB receptors. Combined immunohistochemical and biochemical analyses showed that ET-1 triggered actin cytoskeletal remodeling and a dose-dependent increase in migration (up to 6-fold). Whereas the ETB receptor antagonist (B-BQ788) blunted the ET-1-induced effects, the ETA receptor antagonist (A-BQ123) did not. Moreover, we observed that FNC-B4 cells were independently and selectively stimulated by ET-1 and GnRH. We suggest that ET-1, through ETB receptor activation, may be required to maintain an adequate proliferative stem cell pool in the developing olfactory epithelium and the subsequent commitment to GnRH neuronal migratory pattern. The coordinate interaction between ET receptors and GnRH receptor participates in the fully expressed GnRH-secreting neuron phenotype

Lectin binding in the human foetal testis

In the present study we have investigated the oligosaccharidic content of the glycoconjugates within the human foetal testis starting from its earliest differentiation phase (8, 10 and 12 weeks of gestation). To this purpose we have used a battery of six horseradish peroxidase-labelled lectins (SBA, PNA, WGA, UEAI, LTA and ConA). We have obtained a complete distributional map of the sugar residues of the glycoconjugates in the coelomic mesothelium, tunica albuginea, pre-Sertoli cells, pre-gonocytes, Leydig cells, basement membrane of the sex cords, interstitial tissue, mastocytes and endothelial cells of the capillary vessels. Since the beginning of the testis differentiation phase the cells of the coelomic mesothelium showed a large amount of sugar residues. In the pre-Sertoli cells and in the pre-gonocytes a role played as structural molecules by some oligosaccharides could be hypothesized. Dgalactose-( ß1?3)-N-acetyl-D-galactosamine, sialic acid, N-acetyl-D-glucosamine and a-D-mannose could be involved in inducing and maintaining the cellular activity of the Leydig cells

Distributional map of the terminal and sub-terminal sugar residues of the glycoconjugates in the prepubertal and postpubertal testis of a subject affected by complete androgen insensitivity syndrome (Morris’s syndrome): lectin histochemical study

In the present research we have investigated the distribution of the sugar residues of the glycoconjugates in the prepubertal and postpubertal testes of a subject with Morris’s syndrome (CAIS, Complete Androgen Insensitivity Syndrome). For this purpose a battery of six horseradish peroxidaseconjugated lectins was used (SBA, PNA, WGA, ConA, LTA and UEAI). We have obtained a complete distributional map of the terminal and sub-terminal oligosaccharides in the tunica albuginea, interstitial tissue, lamina propria of the seminiferous tubules, Leydig cells, Sertoli cells, spermatogonia, mastocytes and endothelial cells. Furthermore the present study has shown that a large amount of sugar residues were detectable in the prepubertal and postpubertal testes but that some differences exist with particular regard to the Sertoli cells. The Sertoli cells and the Leydig cells of the retained prepubertal testis of the patient affected by Morris’s syndrome were characterized by the presence of a-L-fucose, which was absent in the retained prepubertal testis of the normal subjects. Comparing the results on the postpubertal testis with those obtained on the same aged testis of healthy subjects we have demonstrated that a-L-fucose in the Sertoli and Leydig cells and D-galactose-N-acetyl-D-galactosamine in the results on the postpubertal testis with those obtained on the same aged testis of healthy subjects we have demonstrated that a-L-fucose in the Sertoli and Leydig cells and D-galactose-N-acetyl-D-galactosamine in the Leydig cells are a unique feature of the subject affected by Morris’s syndrome. D-galactose (ß1?3)-N-acetyl-Dgalactosamine and sialic acid, which are present in the Leydig cells of the normal testis were never observed in the same cells of the postpubertal testis of the CAIS patient

Cadmium induces differentiation of human neuroblasts FNC-B4

Cadmium induces differentiation of human neuroblasts FNC-B

Effetti del cadmio su una linea di neuroblasti umani

Effetti del cadmio su una linea di neuroblasti umani (vedi allegato

The vitamin D receptor agonist BXL-01-0029 as a potential new pharmacological tool for the treatment of inflammatory myopathies

Objective:This study aims to investigatein vitro the effect of the VDR agonist BXL-01-0029 onto IFNc/TNFa-induced CXCL10 secretion by human skeletal muscle cells compared to elocalcitol (VDR agonist), methylprednisolone, methotrexate, cyclosporin A, infliximab and leflunomide; to assessin vivo circulating CXCL10 level in subjects at time of diagnosis with IMs, before therapy, together with TNFa, IFNc, IL-8, IL-6, MCP-1, MIP-1band IL-10, vs. healthy subjects. Methods:Human fetal skeletal muscle cells were used forin vitro studies; ELISA and Bio-Plex were used to measure cell supernatant and IC50determination or serum cytokines; Western blot and Bio-Plex were for cell signaling analysis. Results:BXL-01-0029 decreased with the highest potency IFNc/TNFa-induced CXCL10 protein secretion and targeted cell signaling downstream of TNFain human skeletal muscle cells; CXCL10 level was the highest in sera of subjects diagnosed with IMs before therapy and the only one significantly different vs. healthy controls. Conclusions:Ourin vitro andin vivo data, while confirm the relevance of CXCL10 in IMs, suggested BXL-01-0029 as a novel pharmacological tool for IM treatment, hypothetically to be used in combination with the current immunosuppressants to minimize side effects