MIP-1beta, a novel biomarker for in vitro sensitization test using human monocytic cell line.
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.
Hirota
Morihiko
M
Shiseido Safety and Analytical Research Center, Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa 236-8643, Japan. morihiko.hirota@to.shiseido.co.jp
Moro
Osamu
O
D051940:B7-2 Antigen / Q000032:analysis; D015415:Biomarkers; D002401:Cathepsin B / Q000235:genetics; D002460:Cell Line; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000096:biosynthesis*; D004137:Dinitrochlorobenzene / Q000633:toxicity; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D009532:Nickel / Q000633:toxicity; D020411:Oligonucleotide Array Sequence Analysis; D010655:Phenylenediamines / Q000633:toxicity; D012867:Skin / Q000187:drug effects*
D051940:B7-2 Antigen; D015415:Biomarkers; C066507:CCL4 protein, human; D054407:Chemokine CCL4; D019742:Chemokines, CC; D004137:Dinitrochlorobenzene; D007375:Interleukin-1; D019402:Macrophage Inflammatory Proteins; D010655:Phenylenediamines; C029938:nickel sulfate; D009532:Nickel; D051547:Heme Oxygenase-1; D002401:Cathepsin B; C029728:4-phenylenediamine