title: Betalactam antibiotics affect human dendritic cells maturation through MAPK/NF-kB systems. Role in allergic reactions to drugs.
abstract: The mechanisms leading to drug allergy in predisposed patients, especially those related to T-cell-mediated drug hypersensitivity, are not well understood. A key event in allergic reactions to drugs is the maturation process undergone by dendritic cells (DCs). Although amoxicillin (AX) has been reported to interact and maturate DCs from patients with AX-induced delayed-type hypersensitivity, the cell signaling pathways related to AX-mediated DC maturation have not been elucidated. We sought to determine the role of the MAPK and NF-κΒ pathways on AX-induced DC maturation and functional status. For that purpose, in monocyte-derived-DCs from AX-delayed allergic patients and tolerant subjects, we analyzed the activation pattern of p38MAPK, JNK, and ERK signaling and the NF-κB, maturation markers as well as endocytosis and allostimulatory capacities driven by AX-stimulated-DCs. Our data reveal that AX induces an increase in the phosphorylation levels of the three MAPKs and activated NF-κB in DCs from allergic patients. Moreover, the inhibition of these pathways prevents the up-regulation of surface molecules induced by AX. Additionally, we observed that the allostimulatory capacity and the endocytosis down-regulation in AX-stimulated-DCs from allergic patients depend on JNK and NF-κB activities. Taken together, our data shed light for the first time on the main signaling pathways involved in DC maturation from AX-delayed allergic patient.
authors.affiliation: CABIMER-Andalusian Center for Molecular Biology and Regenerative Medicine, Seville, Spain; Department of Medical Biochemistry, Molecular Biology and Immunology, The University of Seville Medical School, Seville, Spain.
authors.forename: Soledad
authors.initials: S
authors.lastname: Lopez
authors.affiliation: Research Laboratory, IBIMA-Regional University Hospital of Malaga, UMA, Málaga, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Gomez
authors.affiliation: Allergy Service, IBIMA-Regional University Hospital of Malaga, UMA, Málaga, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Torres
authors.affiliation: CABIMER-Andalusian Center for Molecular Biology and Regenerative Medicine, Seville, Spain; Department of Medical Biochemistry, Molecular Biology and Immunology, The University of Seville Medical School, Seville, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Pozo
authors.affiliation: Research Laboratory, IBIMA-Regional University Hospital of Malaga, UMA, Málaga, Spain.
authors.forename: Tahia D
authors.initials: TD
authors.lastname: Fernandez
authors.affiliation: Research Laboratory, IBIMA-Regional University Hospital of Malaga, UMA, Málaga, Spain.
authors.forename: Adriana
authors.initials: A
authors.lastname: Ariza
authors.affiliation: Department of Allergology and Clinical Immunology, University Clinic of Navarra, Pamplona, Spain.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Sanz
authors.affiliation: Allergy Service, IBIMA-Regional University Hospital of Malaga, UMA, Málaga, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Blanca
authors.affiliation: Research Laboratory, IBIMA-Regional University Hospital of Malaga, UMA, Málaga, Spain; Allergy Service, IBIMA-Regional University Hospital of Malaga, UMA, Málaga, Spain. Electronic address: lina.mayorga@ibima.eu.
authors.forename: Cristobalina
authors.initials: C
authors.lastname: Mayorga
mesh_terms: D000328:Adult; D000658:Amoxicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D015536:Down-Regulation; D004342:Drug Hypersensitivity / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation; D047090:beta-Lactams / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D016328:NF-kappa B; D047090:beta-Lactams; D000658:Amoxicillin; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Amoxicillin; Delayed-type hypersensitivity; Dendritic cells; Signaling pathway; T lymphocytes