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
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- 作者：Katrin Sebastian ; Hagen Ott ; Gabriele Zwadlo-Klarwasser ; Claudia Skazik-Voogt ; Yvonne Marquardt ; Katharina Czaja ; Hans F. Merk ; Jens Malte Baron
- 关键词：ADR ; adverse drug reactions ; DTH ; delayed-type hypersensitivity ; DC ; dendritic cell ; IL ; interleukin ; moDC ; monocyte-derived dendritic cells ; LC ; Langerhans cell ; PBMC ; peripheral blood mononuclear cell ; RT-PCR ; reverse transcription polymerase chain reac
- 刊名：Toxicology and Applied Pharmacology
- 出版年：2012
- 出版时间：1 August, 2012
- 年：2012
- 卷：262
- 期：3
- 页码：283-292
- 全文大小：320 K
文摘
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-1¦Â, 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.