Lactosylceramide Mediates the Expression of Adhesion Molecules in TNF-alpha and IFNgamma-stimulated Primary Cultured Astrocytes

Here we have investigated how lactosylceramide (LacCer) modulates gene expression of adhesion molecules in TNF-alpha and IFNgamma (CM)-stimulated astrocytes. We have observed that stimulation of astrocytes with CM increased the gene expression of ICAM-1 and VCAM-1. D-Threo-1-phenyl- 2-decanoylamino-3-morpholino-1-propanol (PDMP) and N-butyldeoxynojirimycin (NBDNJ), inhibitors of glucosylceramide synthase (GLS) and LacCer synthase (galactosyltransferase, GalT-2), inhibited the gene expression of ICAM-1 and VCAM-1 and activation of their gene promoter induced by CM, which were reversed by exogenously supplied LacCer. Silencing of GalT-2 gene using its antisense oligonucleotides also attenuated CM-induced ICAM-1 and VCAM-1 expression, which were reversed by LacCer. PDMP treatment and silencing of GalT-2 gene significantly reduced CM-induced luciferase activities in NF-KB, AP-1, GAS, and STAT-3 luciferase vectors-transfected cells. In addition, LacCer reversed the inhibition of NF-KB and STAT-1 luciferase activities by PDMP. Taken together, our results suggest that LacCer may play a crucial role in the expression of ICAM-1 and VCAM-1 via modulating transcription factors, such as NF-KB, AP-1, STAT-1, and STAT-3 in CM-stimulated astrocytes.

The Clinical and Histopathologic Findings of Lymphonodular Hyperplasia of the Colon in Infancy and Childhood / 대한소아소화기영양학회지

PURPOSE: Lymphonodular hyperplasia of the colon (LNHC) is a rare finding in children and its significance as a pathologic finding is unclear. The aim of this study was to investigate the clinical significance of LNHC by analyzing clinical and histopathologic findings in children with LNHC. METHODS: We analyzed data from 38 patients who were confirmed to have LNHC by colonoscopy. We checked age, birth history, past history, family history, and clinical symptoms. A hematologic exam, stool exam, and image studies were performed and biopsy specimens were examined by a pathologist. All patients were asked to have short- and long-term follow-up. RESULTS: The mean age of the patients was 12.5+/-14.4 months. All patients presented with complaints of bloody stool. They appeared healthy and the hematologic findings were within a normal range, with the exception of one case. There was no other identified source of bleeding. On histologic exam, 36 patients (94.7%) had lymphoid follicles and 34 patients (84.5%) fulfilled the criteria of allergic colitis. Regardless of diet modification and presence of residual symptom, there was no recurrence of bloody stool through long-term follow-up in all patients. CONCLUSION: LNHC is more common in infants who are affected by allergic colitis, but it can appear even after infancy. LNHC should be regarded as the etiology when there are any other causes of rectal bleeding, especially in healthy children. We suggest that LNHC has a benign course regardless of diet modification and it might not require excessive concerns.

Oxidized low density lipoproteins and lactosylceramide both stimulate the expression of proliferating cell nuclear antigen and the proliferation of aortic smooth muscle cells.

We have previously shown that oxidized low density lipoproteins (Ox-LDL) at low concentrations (10 micrograms/ml) via activating a UDP-galactose: glucosylceramide, beta 1-->4 galactosyl-transferase (GalT-2) and producing lactosylceramide can stimulate the proliferation of aortic smooth muscle cells. In this report, we present evidence that Ox-LDL and LacCer, both can induce the expression of proliferating cell nuclear antigen (cyclin). Ox-LDL and LacCer both exerted a time-dependent stimulation of cyclin expression. Maximum increase (3-fold) in cyclin expression occurred between 30-120 min after Ox-LDL/LacCer addition and decreased thereafter. D-threo-l-phenyldecanoylamino-3-morpholino-1-propanol (D-PDMP), an inhibitor of GalT-2, inhibited cell proliferation as well as cyclin expression. This inhibitor also abrogated the Ox-LDL mediated expression of proliferating cell nuclear antigen (cyclin). In contrast, the L-enantiomer of PDMP (L-PDMP) stimulated the expression of cyclin and augmented the Ox-LDL mediated expression of cyclin in these cells. Maximum increase in the expression of cyclin occurred with 20 mumole of L-PDMP and 10 micrograms of Ox-LDL. This overall pattern of Ox-LDL and LacCer mediated regulation is similar to that of the c-fos protooncogenes reported previously by us. We hypothesize that the early induction of GalT-2 may serve as an "Immediate early gene" that plays a role in the signalling cascade by LacCer and involves the kinase c-fos induction and subsequent expression of cyclins. Thus, GalT-2 may play a role in the proliferative response in aortic smooth muscle cells by Ox-LDL.