title: Evaluation of the sensitizing potential of antibiotics in vitro using the human cell lines THP-1 and MUTZ-LC and primary monocyte-derived dendritic cells.
abstract: Since the 7th amendment to the EU cosmetics directive foresees a complete ban on animal testing, alternative in vitro methods have been established to evaluate the sensitizing potential of small molecular weight compounds. To find out whether these novel in vitro assays are also capable to predict the sensitizing potential of small molecular weight drugs, model compounds such as beta-lactams and sulfonamides - which are the most frequent cause of adverse drug reactions - were co-incubated with THP-1, MUTZ-LC, or primary monocyte-derived dendritic cells for 48 h and subsequent expression of selected marker genes (IL-8, IL-1β, CES1, NQO1, GCLM, PIR and TRIM16) was studied by real time PCR. Benzylpenicillin and phenoxymethylpenicillin were recognized as sensitizing compounds because they are capable to induce the mRNA expression of these genes in moDCs and, except for IL-8, in THP-1 cells but not in MUTZ-LC. Ampicillin stimulated the expression of some marker genes in moDCs and THP-1 cells. SMX did not affect the expression of these genes in THP-1, however, in moDCs, at least PIR was enhanced and there was an increase of the release of IL-8. These data reveal that novel in vitro DC based assays might play a role in the evaluation of the allergenic potential of novel drug compounds, but these systems seem to lack the ability to detect the sensitizing potential of prohaptens that require metabolic activation prior to sensitization and moDCs seem to be superior with regard to the sensitivity compared with THP-1 and MUTZ-3 cell lines.
authors.affiliation: Department of Dermatology and Allergology, RWTH Aachen University Hospital, D-52074 Aachen, Germany. ksebastian@ukaachen.de
authors.forename: Katrin
authors.initials: K
authors.lastname: Sebastian
authors.forename: Hagen
authors.initials: H
authors.lastname: Ott
authors.forename: Gabriele
authors.initials: G
authors.lastname: Zwadlo-Klarwasser
authors.forename: Claudia
authors.initials: C
authors.lastname: Skazik-Voogt
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Marquardt
authors.forename: Katharina
authors.initials: K
authors.lastname: Czaja
authors.forename: Hans F
authors.initials: HF
authors.lastname: Merk
authors.forename: Jens Malte
authors.initials: JM
authors.lastname: Baron
mesh_terms: D000667:Ampicillin / Q000009:adverse effects / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology*; D002265:Carboxylic Ester Hydrolases / Q000032:analysis; D002292:Carcinoma, Renal Cell / Q000737:chemistry / Q000378:metabolism; D002352:Carrier Proteins / Q000032:analysis; D002460:Cell Line; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000032:analysis; D003713:Dendritic Cells / Q000737:chemistry / Q000187:drug effects*; D049308:Dioxygenases; D005721:Glutamate-Cysteine Ligase / Q000032:analysis; D006801:Humans; D066298:In Vitro Techniques; D053583:Interleukin-1beta / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D007801:Langerhans Cells / Q000737:chemistry / Q000187:drug effects*; D008264:Macrophages / Q000737:chemistry / Q000187:drug effects*; D009000:Monocytes / Q000737:chemistry / Q000187:drug effects*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis; D010400:Penicillin G / Q000009:adverse effects / Q000494:pharmacology; D010404:Penicillin V / Q000009:adverse effects / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D013420:Sulfamethoxazole / Q000009:adverse effects / Q000494:pharmacology; D014157:Transcription Factors / Q000032:analysis; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D000900:Anti-Bacterial Agents; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D053583:Interleukin-1beta; D016209:Interleukin-8; D009687:Nuclear Proteins; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D000667:Ampicillin; D049308:Dioxygenases; C105340:PIR protein, human; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C117731:TRIM16 protein, human; D044767:Ubiquitin-Protein Ligases; D002265:Carboxylic Ester Hydrolases; C474609:CES1 protein, human; C546365:GCLM protein, human; D005721:Glutamate-Cysteine Ligase; D013420:Sulfamethoxazole; D010400:Penicillin G; D010404:Penicillin V