Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Due to their immunomodulatory functions, mesenchymal stem cells (MSCs) have great potential for clinical applications to prevent rejection in organ transplantation and to prevent graft-versus-host disease in hematopoietic stem cell (HSC) transplantation. Since dendritic cells (DCs) play an important role in modulating diverse T cell responses, including rejection and graft-versus-host disease, the goal of this study was to investigate whether MSCs modulate DC differentiation from HSCs and if this effect could be one of the mechanisms for MSCs' immune-modulating functions. Our results demonstrate that differentiation of HSCs into mature DCs is inhibited in the presence of MSCs. Similar frequency of dendritic precursors in the cultures, either with or without MSCs, suggests that the inhibition of MSCs on the differentiation of mature DCs from HSCs could be due to the arresting of maturation at the dendritic precursor step. Reduced levels of cyclic AMP, adenosine 3',5'-cyclic monophosphate (cAMP) and beta-catenin in DC-like cells from the cocultures are detected, suggesting that induction of apoptosis and inhibition of differentiation could be the basis for the inhibition of mature DCs from HSCs by MSCs. Further, our results demonstrate that DCs derived from HSCs in the presence of MSCs are functionally impaired, especially for those after direct contact with MSCs. To investigate the basis of functional impairment, our data show downregulated tumor necrosis factor-alpha and transforming growth factor-beta1 secretion and upregulated interleukin-6 (IL6) and IL1beta secretion in the cultures with MSCs. Together, MSCs can inhibit differentiation of mature DCs from HSCs by arresting them at the precursor stage and induce their apoptosis. Further, HSC-derived DCs in the presence of MSCs are functionally impaired, which could be partly due to the upregulation of IL6 secretion.
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PMID:Mesenchymal stem cells negatively regulate dendritic lineage commitment of umbilical-cord-blood-derived hematopoietic stem cells: an unappreciated mechanism as immunomodulators. 2054 55

The TiO(2) nanotube layers fabricated by electrochemical anodization have received considerable attention in dentistry and orthopedic medicine due to their increased osseointegration compared with the unanodized titanium. The molecular mechanisms underlying the interactions between nanotubes and osteoblasts is unknown. To examine this, the mRNA expression profile of MG-63 osteoblast-like cells cultured on the TiO(2) nanotubes was explored by DNA microarray. The differentially expressed genes were identified by bioinformatics analysis. Gene ontology (GO) and Go-map network analysis indicated that the TiO(2) nanotubes enhanced osteoblast proliferation and differentiation and decreased osteoblast adhesion and immunization. The expressions of genes were mainly increased in pathways influencing cell proliferation and differentiation (Cell cycle, Terpenoid backbone biosynthesis, and TGF-beta signaling) and were decreased in pathways controlling cell immunization (Cell adhesion molecules (CAMs), Allograft rejection, and Graft-versus-host disease). Signal network analysis generated from differentially expressed genes suggested that CTNNB1 (beta-catenin) was the central gene for increasing osteoblast proliferation and differentiation, and IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) was the central gene for repressing osteoblast immunization on nanotube layers. These two genes were further confirmed by quantitative PCR. The identified signal pathways and central genes in the study are well correlated with osteoblast phenotype. Furthermore, microarray-based bioinformatics analysis is a powerful tool in efficiently understanding molecular mechanisms underlying the interactions between osteoblasts and the nanotube layers.
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PMID:Microarray-based bioinformatics analysis of osteoblasts on TiO2 nanotube layers. 2226 Nov 77