The mechanisms of human renal epithelial cell modulation of autologous dendritic cell phenotype and function

Proximal tubule epithelial cells (PTEC) of the kidney line the proximal tubule downstream of the glomerulus and play a major role in the re-absorption of small molecular weight proteins that may pass through the glomerular filtration process. In the perturbed disease state PTEC also contribute to the inflammatory disease process via both positive and negative mechanisms via the production of inflammatory cytokines which chemo-attract leukocytes and the subsequent down-modulation of these cells to prevent uncontrolled inflammatory responses. It is well established that dendritic cells are responsible for the initiation and direction of adaptive immune responses. Both resident and infiltrating dendritic cells are localised within the tubulointerstitium of the renal cortex, in close apposition to PTEC, in inflammatory disease states. We previously demonstrated that inflammatory PTEC are able to modulate autologous human dendritic cell phenotype and functional responses. Here we extend these findings to characterise the mechanisms of this PTEC immune-modulation using primary human PTEC and autologous monocyte-derived dendritic cells (MoDC) as the model system. We demonstrate that PTEC express three inhibitory molecules: (i) cell surface PD-L1 that induces MoDC expression of PD-L1; (ii) intracellular IDO that maintains the expression of MoDC CD14, drives the expression of CD80, PD-L1 and IL-10 by MoDC and inhibits T cell stimulatory capacity; and (iii) soluble HLA-G (sHLA-G) that inhibits HLA-DR and induces IL-10 expression by MoDC. Collectively the results demonstrate that primary human PTEC are able to modulate autologous DC phenotype and function via multiple complex pathways. Further dissection of these pathways is essential to target therapeutic strategies in the treatment of inflammatory kidney disorders.

A systematic review of community pharmacist therapeutic knowledge of dietary supplements

Background: Internationally, the use of dietary supplements has been growing rapidly. Patient support for pharmacist sales of nutritional and dietary supplements is also strong. The increase in demand for nutritional and dietary supplements and subsequent advice about these products, however, makes it necessary that pharmacists maintain a contemporary knowledge of the area. Aim of review: This systematic review was conducted to examine the current evidence regarding the level of the nutritional and dietary supplement knowledge of community pharmacists and their understanding of their therapeutic effects. Method: Electronic databases including Medline, Scopus, Embase, CINAHL, Scifinder and the Cochrane Controlled Trials Register were searched. Studies assessing nutritional knowledge of pharmacists in community pharmacies were eligible for inclusion. All languages and study designs were considered. Study results were analysed and pharmacist knowledge scores were given out of 100 . Results: From 5594 studies identified, nine met the inclusion criteria. Each study tested pharmacist knowledge with predetermined questions calculating results as the number of questions answered correctly. These knowledge scores were converted to a percentage score for the purpose of this paper. The median knowledge score across all papers was 64%. A lack of studies assessing community pharmacist's knowledge of commonly sold vitamins and minerals was observed. Conclusions Global community pharmacist knowledge of dietary supplements appears to be poor. Community pharmacists have an professional responsibility to provide accurate health information about dietary supplements as they do for any other therapies they provide to patients. Further research including that which assesses pharmacist's therapeutic knowledge of commonly sold vitamins and minerals is suggested.