ABSTRACT
Antimicrobial peptides (AMPs) are small molecules with microbicidal and immunoregulatory activities. In this study we evaluated the anti-inflammatory and antimicrobial activities of peptides ToAP3 and ToAP4, AMPs from the venom of the Brazilian scorpion Tityus obscurus. To test the peptides' activity, murine bone marrow-derived macrophages (BMDMs) or dendritic cells (BMDCs) were stimulated with peptides plus LPS to analyze their ability to modulate cytokine release as well as phenotypic markers. For antimicrobial analysis, we evaluated the indirect activity against macrophage-internalized Cryptococcus neoformans and direct activity against Mycobacterium massiliense. Our data demonstrate that they were able to reduce TNF-α and IL-1ß transcript levels and protein levels for BMDM and BMDC. Furthermore, the reduction of TNF-α secretion, before LPS- inflammatory stimuli, is associated with peptide interaction with TLR-4. ToAP4 increased MHC-II expression in BMDC, while ToAP3 decreased co-stimulatory molecules such as CD80 and CD86. Although these peptides were able to modulate the production of cytokines and molecules associated with antigen presentation, they did not increase the ability of clearance of C. neoformans by macrophages. In antimicrobial analysis, only ToAP3 showed potent action against bacteria. Altogether, these results demonstrate a promising target for the development of new immunomodulatory and anti-bacterial therapies.
Subject(s)
Anti-Infective Agents/pharmacology , Cytokines/metabolism , Peptides/pharmacology , Scorpion Venoms/chemistry , Scorpions , Toll-Like Receptor 4/antagonists & inhibitors , Animals , Anti-Infective Agents/isolation & purification , Anti-Inflammatory Agents, Non-Steroidal/isolation & purification , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cell Line , Cryptococcus neoformans/drug effects , Dendritic Cells/drug effects , Dendritic Cells/immunology , Immunity, Innate/drug effects , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/immunology , Mice, Inbred C57BL , Mice, Knockout , Microbial Sensitivity Tests , Mycobacterium abscessus/drug effects , Peptides/isolation & purification , Toll-Like Receptor 4/geneticsABSTRACT
The beam quality correction factor kQ,Q0 and the perturbation factor pQ for photon beams were calculated for the NE2571A and NE2581A ionization chambers, using the Monte Carlo simulation code PENELOPE. Results are compared to those quoted for the NE2571 and NE2581 chambers in previous works. Both kQ,Q0 and pQ obtained for NE2571A and NE2581A chambers agree with those of their predecessors NE2571 and NE2581 ones.
Subject(s)
Radiometry/instrumentation , Radiometry/methods , Algorithms , Computer Simulation , Electrodes , Equipment Design , Graphite/chemistry , Ions , Monte Carlo Method , Particle Accelerators , Photons , Polytetrafluoroethylene/chemistry , Quality Control , Radiotherapy/methods , Reference Values , SoftwareABSTRACT
The beam quality correction factor [Formula: see text] and the perturbation factor pQ, commonly considered in dosimetry with ionization chambers, were calculated for the NE2571 and the Standard Imaging A19 and A12S chambers, using the Monte Carlo simulation code PENELOPE. For the NE2571 chamber, the values of [Formula: see text] obtained are in very good agreement with those found in previous works by Wulff et al. and Muir and Rogers with the code EGSnrc and also with the experimental results summarized in the NCS code of practice. For pQ, a difference of â¼0.4% has been found between our results and those obtained with EGSnrc for (60)Co and this difference increases slightly with TPR10(20) values. These factors have been calculated also for the A19 and A12S chambers of Standard Imaging. The values of [Formula: see text] show reasonable agreement with those recently calculated by Muir and Rogers and the measurements of McEwen.
