Journal of Clinical Toxicology
Open Access

Co-culture of immortalized keratinocytes and immune cells to investigate sulfur mustard toxicity and potential treatments

4^th Global Summit on Toxicology

August 24-26, 2015 Philadelphia, USA

F Balszuweit, G Menacher, A Schmidt, F Worek, H Thiermann and D Steinritz

Scientific Tracks Abstracts: J Clin Toxicol

Abstract :

Sulfur Mustard (SM) is a chemical warfare agent, causing skin blistering, inflammation and impaired wound healing. Due to its
complex effects, no causative antidote has been established despite decades of medical research. Advanced cell culture studies may
provide new insights to significantly improve future therapeutic options. HaCaT cells, immortalized keratinocytes were co-cultivated
with THP-1 (a monocyte-derived cell line) and exposed to SM. 2% THP-1, similar to ratio of resident immune cells in human
skin in vivo, resulted in a strong increase of necrosis, apoptosis and inflammation after SM exposure. Further increase of THP-1
concentrations had little additional effects. It was, thus, demonstrated that immune cells, when exposed to SM have an aggravating
effect on SM toxicity. Co-culture of HaCaT with 2% THP-1 takes the effect of immune cells into account, is a closer approximation of
in vivo conditions and thus a more valid test system, compared to HaCaT monocultures. Anti-inflammatory compounds, including
dexamethasone and two NSAIDs (ibuprofen and diclofenac) were tested, both in HaCaT monocultures and HaCaT-THP-1 coculture
after SM exposure. Dexamethasone had some protective effects in the monocultures, but these effects were less pronounced
in co-cultures. In contrast, diclofenac, having shown only negligible effects in monocultures demonstrated highly protective effects in
co-cultures. Ibuprofen however, had aggravating effects on SM toxicity in monocultures and these effects even worse in co-cultures.
In summary, our results demonstrate that effects of immune cells have to be taken into consideration when studying SM toxicity in
cell cultures. Use of HaCaT-THP-1 co-culture can provide new insight into efficacy and safety of potential antidotes.

Biography :

F Balszuweit is a pharmacist and obtained his PhD at the Free University Berlin in 2005. Along with his research activities within the Bundeswehr Medical Service, he has
been concerned with research management, regulatory affairs and scientific cooperation. His research interests are focused on cell co-cultures to identify novel treatment
strategies, in particular against sulfur mustard injuries.