1. Synergistic effect between amoxicillin and TLR ligands on dendritic cells from amoxicillin-delayed allergic patients
- Author
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Lidia Melendez, Tahia D. Fernandez, Adriana Ariza, María José Torres, Inmaculada Doña, Ana Belen Blazquez, Miguel Blanca, Cristobalina Mayorga, Maria J. Sanchez-Quintero, Inmaculada Andreu, Enrique J. Gómez, [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., This work was supported by grants from: the Carlos III (ISCIII PS09/00966, PI12/02481 and PI12/02529), Junta de Andalucía (PI-0199/2007, PI-0180/2008, CTS-7433 and CTS 06603), and FIS-Thematic Networks and Co-operative Research Centres: RIRAAF (RD07/0064, and RD12/0013). The BBSSPA, Carlos Haya Hospital Unit is supported by Instituto de Salud Carlos III, Spanish Health Ministry (Grant nº RD09/0076/00112)' and the board of health ministry of Andalusia.
- Subjects
Male ,Células dendríticas ,medicine.medical_treatment ,Lymphocyte proliferation ,Pharmacology ,Chemicals and Drugs::Chemical Actions and Uses::Specialty Uses of Chemicals::Laboratory Chemicals::Ligands [Medical Subject Headings] ,Monocytes ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Pharmacological Processes::Drug Interactions::Drug Synergism [Medical Subject Headings] ,Cells, Cultured ,Amoxicilina ,Multidisciplinary ,medicine.diagnostic_test ,Chemistry ,Linfocitos ,Imidazoles ,Citocinas ,Middle Aged ,Humanos ,Cytokine ,Medicine ,Cytokines ,Female ,Drug Eruptions ,Research Article ,Diseases::Skin and Connective Tissue Diseases::Skin Diseases::Exanthema [Medical Subject Headings] ,Adult ,Sinergismo medicamentoso ,Science ,Flow cytometry ,Hipersensibilidad retardada ,Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::Penicillins::Penicillin G::Ampicillin::Amoxicillin [Medical Subject Headings] ,Immune system ,Antigen ,Diseases::Immune System Diseases::Hypersensitivity::Hypersensitivity, Delayed [Medical Subject Headings] ,Exantema ,medicine ,Hypersensitivity ,Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes [Medical Subject Headings] ,Humans ,Ligandos ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intercellular Signaling Peptides and Proteins::Cytokines [Medical Subject Headings] ,Anatomy::Cells::Antigen-Presenting Cells::Dendritic Cells [Medical Subject Headings] ,TLR9 ,Amoxicillin ,TLR7 ,Dendritic Cells ,Toll-Like Receptor 2 ,TLR2 ,Immunology - Abstract
Journal Article; 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. Yes
- Published
- 2013