Thiram (
TMTD) is a widely used dithiocarbamate
pesticide and fungicide and is one of potent contact
allergens. In the light of known properties,
thiram is also considered to be used as an inhibitor of
inflammation. To investigate whether known pro-oxidative properties of
thiram might be involved in immunogenic mechanisms, we carried out an in vitro study aimed at analysis of
reactive oxygen species (ROS) generation, activation of NF-κB, expression of iNOS and COX-2, production of NO,
PGE2 and IL-1β in murine macrophage cells (RAW 264.7). The cells were treated by
thiram alone (0.5 µg/mL; 2 μM and 2 µg/mL; 8 μM) or concomitantly with bacterial
endotoxin (LPS; 1 μg/mL). LPS was used as an
endotoxin that triggers changes characteristic for inflammatory state of the cell.
TMTD increased ROS production, level of
oxidized glutathione (
GSSG) and activated NF-κB. The consequence of NF-κB activation was the increase of IL-1β and NO production characteristic for
inflammation. However, we did not observe changes in
PGE2 concentration. We observed expression of iNOS, COX-2
proteins and NO and
PGE2 production in macrophages treated with
thiram concomitantly with LPS lower than those in cells stimulated with LPS alone.
Thiram (2 µg/mL) decreased NF-κB activation and production of LPS-induced IL-1β. In conclusion, we demonstrated changes induced by
TMTD characteristic for
inflammation. Hence, it can be supposed that they may participate in the elicitation phase of
allergic contact dermatitis induced by
thiram. However, when
TMTD acts concomitantly with LPS, it decreases the intensity of
inflammation state in RAW 264.7.