PMID- 31376652 OWN - NLM STAT- MEDLINE DCOM- 20200213 LR - 20200213 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 118 DP - 2019 Oct TI - Peptides ToAP3 and ToAP4 decrease release of inflammatory cytokines through TLR-4 blocking. PG - 109152 LID - S0753-3322(19)32234-6 [pii] LID - 10.1016/j.biopha.2019.109152 [doi] AB - 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-alpha and IL-1beta transcript levels and protein levels for BMDM and BMDC. Furthermore, the reduction of TNF-alpha 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. CI - Copyright (c) 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved. FAU - Veloso Junior, Paulo Henrique de Holanda AU - Veloso Junior PHH AD - Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil. FAU - Simon, Karina Smidt AU - Simon KS AD - Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil. FAU - de Castro, Raffael Junio Araujo AU - de Castro RJA AD - Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil. FAU - Coelho, Luisa Coutinho AU - Coelho LC AD - Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil. FAU - Erazo, Fabian Andres Hurtado AU - Erazo FAH AD - Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil. FAU - de Souza, Adolfo Carlos Barros AU - de Souza ACB AD - Department of Physiological Sciences, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil. FAU - das Neves, Rogerio Coutinho AU - das Neves RC AD - Department of Biosciences and Technologies, Institute of Tropical Diseases and Public Health, Federal University of Goias, Goiania, Brazil. FAU - Lozano, Viviane Furlan AU - Lozano VF AD - Public Health Central Laboratory, Secretary of Health of Distrito Federal, Brasilia, Brazil. FAU - Schwartz, Elizabeth Ferroni AU - Schwartz EF AD - Department of Physiological Sciences, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil. FAU - Tavares, Aldo Henrique AU - Tavares AH AD - Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil. FAU - Mortari, Marcia Renata AU - Mortari MR AD - Department of Physiological Sciences, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil. FAU - Junqueira-Kipnis, Ana Paula AU - Junqueira-Kipnis AP AD - Department of Biosciences and Technologies, Institute of Tropical Diseases and Public Health, Federal University of Goias, Goiania, Brazil. FAU - Silva-Pereira, Ildinete AU - Silva-Pereira I AD - Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil. FAU - Bocca, Anamelia Lorenzetti AU - Bocca AL AD - Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil. Electronic address: albocca@unb.br. LA - eng PT - Journal Article DEP - 20190731 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Anti-Infective Agents) RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Cytokines) RN - 0 (Peptides) RN - 0 (Scorpion Venoms) RN - 0 (Tlr4 protein, mouse) RN - 0 (Toll-Like Receptor 4) SB - IM MH - Animals MH - Anti-Infective Agents/isolation & purification/*pharmacology MH - Anti-Inflammatory Agents, Non-Steroidal/isolation & purification/pharmacology MH - Cell Line MH - Cryptococcus neoformans/drug effects MH - Cytokines/*metabolism MH - Dendritic Cells/drug effects/immunology MH - Immunity, Innate/drug effects MH - Macrophages, Peritoneal/drug effects/immunology MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Microbial Sensitivity Tests MH - Mycobacterium abscessus/drug effects MH - Peptides/isolation & purification/*pharmacology MH - Scorpion Venoms/*chemistry MH - *Scorpions MH - Toll-Like Receptor 4/*antagonists & inhibitors/genetics OTO - NOTNLM OT - Anti-inflammatory OT - Dendritic cells OT - Macrophages OT - Scorpion venom OT - Tityus Obscurus OT - ToAP3 OT - ToaP4 EDAT- 2019/08/04 06:00 MHDA- 2020/02/14 06:00 CRDT- 2019/08/04 06:00 PHST- 2019/05/13 00:00 [received] PHST- 2019/06/08 00:00 [revised] PHST- 2019/06/17 00:00 [accepted] PHST- 2019/08/04 06:00 [pubmed] PHST- 2020/02/14 06:00 [medline] PHST- 2019/08/04 06:00 [entrez] AID - S0753-3322(19)32234-6 [pii] AID - 10.1016/j.biopha.2019.109152 [doi] PST - ppublish SO - Biomed Pharmacother. 2019 Oct;118:109152. doi: 10.1016/j.biopha.2019.109152. Epub 2019 Jul 31.