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Title: Synergistic Effect between Amoxicillin and TLR Ligands on Dendritic Cells from Amoxicillin-Delayed Allergic Patients.
Authors: Sanchez-Quintero, Maria J
Torres, Maria J
Blazquez, Ana B
Gómez, Enrique
Fernandez, Tahia D
Doña, Inmaculada
Ariza, Adriana
Andreu, Inmaculada
Melendez, Lidia
Blanca, Miguel
Mayorga, Cristobalina
metadata.dc.contributor.authoraffiliation: [Sanchez-Quintero,MJ; Blazquez,AB; Gómez,E; Fernandez,TD; Mayorga,C] Research Laboratory, Carlos Haya Hospital-IBIMA, Málaga, Spain. [Torre,MJ; Doña,I; Blanca,M; Mayorga,C] Allergy Service Carlos Haya Hospital-IBIMA, Málaga, Spain. [Andreu,I] Joint Research Unit IIS La Fe and Polytechnical University of Valencia, Spain. Institute of Chemical Technology UPV-CSIC, Polytechnical University of Valencia, Valencia, Spain.
Keywords: Amoxicilina;Células dendríticas;Ligandos;Sinergismo medicamentoso;Hipersensibilidad retardada;Linfocitos;Citocinas;Exantema;Humanos
metadata.dc.subject.mesh: Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Penicillins::Penicillin G::Ampicillin::Amoxicillin
Medical Subject Headings::Anatomy::Cells::Antigen-Presenting Cells::Dendritic Cells
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Specialty Uses of Chemicals::Laboratory Chemicals::Ligands
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Pharmacological Processes::Drug Interactions::Drug Synergism
Medical Subject Headings::Diseases::Immune System Diseases::Hypersensitivity::Hypersensitivity, Delayed
Medical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines
Medical Subject Headings::Diseases::Skin and Connective Tissue Diseases::Skin Diseases::Exanthema
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Issue Date: 16-Sep-2013
Publisher: Public Library of Science
Citation: Sanchez-Quintero MJ, Torres MJ, Blazquez AB, Gómez E, Fernandez TD, Doña I, et al. Synergistic Effect between Amoxicillin and TLR Ligands on Dendritic Cells from Amoxicillin-Delayed Allergic Patients. PLoS ONE. 2013; 8(9):e74198
Abstract: Amoxicillin, a low-molecular-weight compound, is able to interact with dendritic cells inducing semi-maturation in vitro. Specific antigens and TLR ligands can synergistically interact with dendritic cells (DC), leading to complete maturation and more efficient T-cell stimulation. The aim of the study was to evaluate the synergistic effect of amoxicillin and the TLR2, 4 and 7/8 agonists (PAM, LPS and R848, respectively) in TLR expression, DC maturation and specific T-cell response in patients with delayed-type hypersensitivity (DTH) reactions to amoxicillin. Monocyte-derived DC from 15 patients with DTH to amoxicillin and 15 controls were cultured with amoxicillin in the presence or absence of TLR2, 4 and 7/8 agonists (PAM, LPS and R848, respectively). We studied TLR1-9 gene expression by RT-qPCR, and DC maturation, lymphocyte proliferation and cytokine production by flow cytometry. DC from both patients and controls expressed all TLRs except TLR9. The amoxicillin plus TLR2/4 or TLR7/8 ligands showed significant differences, mainly in patients: AX+PAM+LPS induced a decrease in TLR2 and AX+R848 in TLR2, 4, 7 and 8 mRNA levels. AX+PAM+LPS significantly increased the percentage of maturation in patients (75%) vs. controls (40%) (p=0.036) and T-cell proliferation (80.7% vs. 27.3% of cases; p=0.001). Moreover, the combinations AX+PAM+LPS and AX+R848 produced a significant increase in IL-12p70 during both DC maturation and T-cell proliferation. These results indicate that in amoxicillin-induced maculopapular exanthema, the presence of different TLR agonists could be critical for the induction of the innate and adaptive immune responses and this should be taken into account when evaluating allergic reactions to these drugs.
Description: Journal Article;
metadata.dc.identifier.doi: 10.1371/journal.pone.0074198
ISSN: 1932-6203 (Online)
Appears in Collections:01- Artículos - Hospital Regional de Málaga

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