Immortalized human keratinocytes: A model system to study the efficacy of therapeutic drugs in response to the chemical warfare agent sulfur mustard (HD)
Keywords: chemical agent, human keratinocytes,interlukin-8, simian virus 40, sulfur mustard.
# MCHK-CI, Bldg 40 Dept of Clinical Investigation,
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.
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