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Janna Nousbeck,
A Ishida-Yamamoto,
Miri Bidder,
Dana Fuchs,
Katja Eckl,
Hans Christian Hennies,
Nadav Sagiv,
Andrea Gat,
Meri Gini, Irina Filip,
Hagit Matz,
Ilan Goldberg,
Claes D Enk,
Ofer Sarig,
Benny Meilik,
Daniel Aberdam,
Amos Gilhar,
Eli Sprecher
Journal of Investigative Dermatology 05/2011; 131(8):1767-70. · 6.31 Impact Factor
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ABSTRACT: It was the aim of this study to evaluate the number of 2 lymphoid subpopulations, CD8(+) cells and FOXP3(+), in the duodenum mucosa from pediatric celiac patients.
Tissue sections prepared from paraffin-embedded biopsies of the descending duodenum of 61 celiac patients with Marsh grade 1 (M1), M2 and M3 disease and biopsies from 21 age-matched non-celiac (NC) patients were immunohistostained with anti-CD8 or FOXP3 antibodies.
The histological Marsh grade correlated with the mean number of FOXP3(+) cells in the lamina propria (LP) mucosa (8.9 ± 1.1, 6.8 ± 2.4, 24.5 ± 2.6 and 31.1 ± 2.8 for NC, M1, M2 and M3 biopsies, respectively; p < 0.001). Using a cutoff point of 15 cells, 95% of NC and 88% of M1 biopsies had a mean of <15 FOXP3(+) cells compared with 14% for M2 and 13% for M3 biopsies. The number of FOXP3(+) cells in the epithelial mucosa also correlated with transglutaminase type 2 serum levels from the celiac patients. Unlike the FOXP3(+) cells, CD8(+) lymphocytes were present in both LP and surface epithelial mucosa and significantly different only in the LP mucosa of the M2 and M3 groups.
The number of FOXP3(+) cells is substantially increased in the mucosa of celiac patients at advanced stages. Characterization of the activity of these cells in celiac and in other inflammatory bowel diseases will enable us to understand the significance of these cells in celiac disease.
Pathobiology 01/2010; 77(6):328-34. · 1.18 Impact Factor
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ABSTRACT: Galectin-3, an endogenous pleiotropic beta-galactoside-binding protein, which is expressed by various malignant and normal cells, regulates many biological and pathological processes, including inflammation. In the present study, we tested a possible correlation between the severity of pouchitis in patients with ulcerative colitis who underwent ileal pouch-anal anastomosis (IPAA) and the presence of galectin-3(+) macrophages in pouch mucosa. Paraffin-embedded pouch biopsies from patients with normal pouch function or chronic and recurrent acute pouchitis were immunohistostained with galectin-3, CD68, and smooth muscle actin (SMA) antibodies. Microscopic examination was performed in a blinded fashion. There was a significant decrease in the staining index of galectin-3 in the subepithelial macrophages in patients with chronic pouchitis (0.53, P=0.001; n=12) or recurrent acute pouchitis (0.43, P=0.008; n=10) when compared to patients with no clinical manifestations of pouchitis (0.63, n=12). No significant differences were noted in the lamina propria of small intestine biopsies from the same patients (from 0.63 to 0.68, P=0.24). Galectin-3 staining was restricted to CD68(+) macrophages and not present in myofibroblasts. Clinical manifestation of pouchitis is inversely correlated with galectin-3 expression in the pouches' subepithelial lamina propria macrophages.
Pathology - Research and Practice 04/2009; 205(8):551-8. · 1.21 Impact Factor
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ABSTRACT: Peroxisome proliferator-activated receptor (PPAR) agonists were shown to inhibit atherosclerosis through augmentation of endothelial nitric oxide synthase (eNOS) activity. In addition, rosiglitazone exerts a beneficial effect in chronic renal failure (CRF). Since l-arginine transport by CAT-1 (the specific arginine transporter for eNOS) is inhibited in uremia, we aimed to explore the effect of rosiglitazone on arginine transport in CRF. Arginine uptake by aortic rings was studied in control animals, rats, 6 wk following 5/6 nephrectomy (CRF) and rats with CRF treated with rosiglitazone. The decrease of arginine transport in CRF was prevented by rosiglitazone. Immunobloting revealed that CAT-1 protein was decreased in CRF but remained unchanged following rosiglitazone administration. Protein content of the membrane fraction of PKCalpha and phosphorylated CAT-1 increased significantly in CRF, effects that were prevented by rosiglitazone. PKCalpha phosphorylation was unchanged but significantly attenuated by rosiglitazone in CRF. Ex vivo administration of phorbol-12-myristate-13-acetate to rosiglitazone-treated CRF rats significantly attenuated the effect of rosiglitazone on arginine uptake. The decrease in cGMP response to carbamyl-choline (eNOS agonist) was significantly attenuated by rosiglitazone in CRF. Western blotting and immunohistochemistry analysis revealed that protein nitration was intensified in the endothelium of CRF rats and this was attenuated by rosiglitazone. In conclusion, rosiglitazone prevents the decrease in arginine uptake in CRF through both depletion and inactivation of PKCalpha. These findings are associated with restoration of eNO generation and attenuation of protein nitration and therefore may serve as a novel mechanism to explain the beneficial effects of rosiglitazone on endothelial function in uremia.
American journal of physiology. Renal physiology 08/2008; 295(2):F471-7. · 3.68 Impact Factor
