Immortalized human keratinocytes: A model system to study

0,35

MB

the efficacy of therapeutic drugs in response to the chemical

6

stron

warfare agent sulfur mustard (HD)

2317

ID

U.S. Army Medical Research Institute of Chemical Defense

2004

rok

Cytokines have been established as biomarkers to detect exposure of cells to chemical warfare

agents such as sulfur mustard (2,2'-dichlorodiethyl sulfide, HD). In this study cultured normal and

SV40 immortalized human epidermal keratinocyte (NHEK/IHEK) cells were compared as potential

model systems to measure the efficacy of therapeutic drugs against HD. Immortalized human

epidermal keratinocytes resemble their primary cell counterparts but have the advantage of being

carried through long-term culture. Immortalized cells also provide consistency and durability and are

less costly than primary keratinocytes. Immunoassay studies were performed to examine the

response of these two cell lines to HD. We found that both normal and immortalized NHEKs

secreted the pro-inflammatory mediator interleukin-8 (IL-8) when exposed to HD. However, a major

difference was observed between the NHEK cell line 6207 and IHEK cell line 425. IHEK cell line 425

produced higher levels of Interleuken-8 then those of its normal counterpart cell line 6207. This

observation is significant since therapeutic drugs such as ibuprofen, which depress cytokine

production, may not allow these biomarkers to be detected efficiently in experimental analysis of

certain NHEK cell lines. The fact that Il-8 production higher in cell line 425 cell makes this in vitro

model a potential screening tool to study the efficacy of drugs that suppress production of

cytokine markers.