/pdf/a-toll-like-receptor-recognizes-bacterial-dna-2lif1icvoq.pdf

A Toll-like receptor recognizes bacterial DNA

Damage-associated molecular patterns (DAMPs) include endogenous intracellular molecules released by activated or necrotic cells and extracellular matrix (ECM) molecules that are upregulated upon injury or degraded following tissue damage. DAMPs are vital danger signals that alert our immune system to tissue damage upon both infectious and sterile insult. DAMP activation of Toll-like receptors (TLRs) induces inflammatory gene expression to mediate tissue repair. However, DAMPs have also been implicated in diseases where excessive inflammation plays a key role in pathogenesis, including rheumatoid arthritis (RA), cancer, and atherosclerosis. TLR activation by DAMPs may initiate positive feedback loops where increasing tissue damage perpetuates pro-inflammatory responses leading to chronic inflammation. Here we explore the current knowledge about distinct signalling cascades resulting from self TLR activation. We also discuss the involvement of endogenous TLR activators in disease and highlight how specifically targeting DAMPs may yield therapies that do not globally suppress the immune system.

Dampening inflammation by modulating tlr signalling

Tumor-associated macrophage/microglia infiltration in human gliomas is correlated with MCP-3, but not MCP-1

Objective
To explore the effects of all-trans retinoic acid(ATRA)on glioma stem cell phenotype.


Methods
The glioma stem cell(GSC)from surgically resected human glioma specimens were isolated and enriched by neurosphere assay and then its differentiation was induced with all-trans retinoic acid(ATRA,1μmol/L)for 1 week.Markers were determined by flow cytometry,Western blot and reverse transcription-polymerase chain reaction(RT-PCR).Side population cells were analyzed by flow cytometry.Growth characteristics were detected by neurosphere formation assay and cell cycle analysis.GSC and the differentiated cells(1×105)were implanted stereotactically and intracranially into the Balb/c nude mice to compare the survival time.All data were analyzed with the SPSS software version 17.0.


Results
ATRA potently induced the differentiation of GSC and reduced glioma stem cell phenotype.And there were an elevated expression of glial fibrillary acidic protein(GFAP)and a reduced expression of such stem cell makers as CD133 and Nestin.The side population rate decreased.ATRA inhibited the neurosphere formation of GSC and induced the arrest of cell growth.ATRA could prolong the survival time.


Conclusion
GSC may be differentiated efficiently by ATRA.The stemness of GSC decreases obviously after the differentiation of ATRA and the survival time is prolonged.Thus ATRA may be applied for targeted therapies of glioma stem cell.


Key words: 
Tretinoinacid; Differentiation; Glioma; Stemcell

[Differentiation treatment by all-trans retinoic acid reduces phenotype of glioma stem cells].

Dissecting the role of Toll-like receptors in microglia-glioma crosstalk

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Dissecting the role of Toll-like receptors in microglia-glioma crosstalk