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Hirota M, Moro O: MIP-1beta, a novel biomarker for in vitro sensitization test using human monocytic cell line. Toxicol In Vitro. 2006 Aug;20(5):736-42. Epub 2005 Nov 28. In order to seek a novel biomarker for predicting skin sensitization, changes in the gene expression profile of THP-1 cells on exposure to 2,4-dinitrochlorobenzene (DNCB), p-phenylenediamine (pPD) and nickel sulfate (Ni) were assessed using oligo-DNA microarrays. While the change in gene expression varied depending on the sensitizers, up-regulation of MIP-1 beta mRNA expression was detected in both DNCB-treated and Ni-treated THP-1 cells. This finding was validated by RT-PCR and confirmed at the protein level by ELISA. Secretion of MIP-1 beta from THP-1 was detected after 24-h treatment with sensitizers such as DNCB, Ni, 2-mercaptobenzothiazole (2-MBT) and cobalt sulfate (Co), while pPD and non-sensitizers such as sodium dodecyl sulfate (SDS) and benzalkonium chloride (BC) had no effect. The use of both MIP-1 beta production and CD86 expression as criteria reduced the number of false-negatives, and the results were in good agreement with those of in vivo assays. MIP-1 beta may be useful as a novel biomarker in in vitro sensitization assay using THP-1 cells, either alone or in combination with known markers. |
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