The glycoprotein-hormones activin A and inhibin A interfere with dendritic cell maturation

<p>Abstract</p> <p>Background</p> <p>Pregnancy represents an exclusive situation in which the immune and the endocrine system cooperate to prevent rejection of the embryo by the maternal immune system. While immature dendritic cells (iDC) in the early pregnancy decidua presumably contribute to the establishment of peripheral tolerance, glycoprotein-hormones of the transforming growth factor beta (TGF-beta) family including activin A (ActA) and inhibin A (InA) are candidates that could direct the differentiation of DCs into a tolerance-inducing phenotype.</p> <p>Methods</p> <p>To test this hypothesis we generated iDCs from peripheral-blood-monocytes and exposed them to TGF-beta1, ActA, as well as InA and Dexamethasone (Dex) as controls.</p> <p>Results</p> <p>Both glycoprotein-hormones prevented up-regulation of HLA-DR during cytokine-induced DC maturation similar to Dex but did not influence the expression of CD 40, CD 83 and CD 86. Visualization of the F-actin cytoskeleton confirmed that the DCs retained a partially immature phenotype under these conditions. The T-cell stimulatory capacity of DCs was reduced after ActA and InA exposure while the secretion of cytokines and chemokines was unaffected.</p> <p>Conclusion</p> <p>These findings suggest that ActA and InA interfere with selected aspects of DC maturation and may thereby help preventing activation of allogenic T-cells by the embryo. Thus, we have identified two novel members of the TGF-beta superfamily that could promote the generation of tolerance-inducing DCs.</p

Multi-year interlaboratory exercises for the analysis of illicit drugs and metabolites in wastewater:development of a quality control system

Thirty-seven laboratories from 25 countries present the development of an inter-laboratory testing scheme for the analysis of seven illicit drug residues in standard solutions, tap- and wastewater. Almost 10 000 concentration values were evaluated: triplicates of up to five samples and 26 laboratories per year. The setup was substantially improved with experiences gained across the six repetitions (e.g. matrix type, sample conditions, spiking levels). From this, (pre-)analytical issues (e.g. pH adjustment, filtration) were revealed for specific analytes which resulted in formulation of best-practice protocols for inter-laboratory setup and analytical procedures. The results illustrate the effectiveness of the inter-laboratory setup to assess laboratory performance in the framework of wastewater-based epidemiology. The exercise proved that measurements of laboratories were of high quality (>80% satisfactory results for six out of seven analytes) and that analytical follow-up is important to assist laboratories in improving robustness of wastewater-based epidemiology results

Improving wastewater-based epidemiology to estimate cannabis use:focus on the initial aspects of the analytical procedure

Wastewater-based epidemiology is a promising and complementary tool for estimating drug use by the general population, based on the quantitative analysis of specific human metabolites of illicit drugs in urban wastewater. Cannabis is the most commonly used illicit drug and of high interest for epidemiologists. However, the inclusion of its main human urinary metabolite 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THC-COOH) in wastewater-based epidemiology has presented several challenges and concentrations seem to depend heavily on environmental factors, sample preparation and analyses, commonly resulting in an underestimation. The aim of the present study is to investigate, identify and diminish the source of bias when analysing THC-COOH in wastewater. Several experiments were performed to individually assess different aspects of THC-COOH determination in wastewater, such as the number of freeze-thaw cycles, filtration, sorption to different container materials and in-sample stability, and the most suitable order of preparatory steps. Results highlighted the filtration step and adjustment of the sample pH as the most critical parameters to take into account when analysing THC-COOH in wastewater. Furthermore, the order of these initial steps of the analytical procedure is crucial. Findings were translated into a recommended best-practice protocol and an inter-laboratory study was organized with eight laboratories that tested the performance of the proposed procedure. Results were found satisfactory with z-scores ≤ 2

Mycobacterium tuberculosis heat-shock protein 70 impairs maturation of dendritic cells from bone marrow precursors, induces interleukin-10 production and inhibits T-cell proliferation in vitro

In different inflammatory disease models, heat-shock proteins (hsp) and hsp-derived peptides have been demonstrated to possess anti-inflammatory properties. While some studies have shown that hsp can directly interact with antigen-presenting cells, others report that bacterial hsp can induce specific T cells with regulatory phenotypes. Effective characterization of the immunomodulatory effects of hsp 70, however, has historically been confounded by lipopolysaccharide (LPS) contamination. In this study, we compared the effects of LPS-free Mycobacterial tuberculosis hsp 70 (TBhsp70) and its possible contaminants on dendritic cells (DC). We demonstrate herein that LPS-free TBhsp70 inhibits murine DC maturation in vitro, while LPS-contaminated TBhsp70 induces DC maturation. Mock recombinant preparations have no effect. In contrast to LPS, TBhsp70 does not induce tumour necrosis factor-α production by DC, but interleukin-10. In vivo, only LPS-contaminated TBhsp70 induces up-regulation of CD86 in splenic mature DC. Finally, TBhsp70 inhibited phytohaemagglutinin-induced T-cell proliferation. Our results support the hypothesis that TBhsp70 does not have inflammatory potential, but rather has immunosuppressive properties