Effects of diazinon on mast cell activation

[Speaker] Kyohka Tanaka:1
[Co-author] Miyoko Matsushima:1, Kazuko Atsumi:1, Kanako Sasou:1, Tomoshi Sugiyama:2, Tomoko Ohdachi:3, Jun Ueyama:1, Naozumi Hashimoto:3, Tsutomu Kawabe:1
1:Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Japan, 2:Department of Thoracic Surgery, Nagoya University Graduate School of Medicine, Japan, 3:Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Japan

Diazinon is one of the organophosphorus (OP) insecticides and heavily used not only in agriculture, but also for home gardening and indoor pest control in Japan. Diazinon has been reported to increase TNF-alpha production in rat serum and brain, suggesting that diazinon can modify the immune response. Although various alternative molecular targets and mechanisms of OP insecticides have been reported, less is known about the target cells or target molecules of diazinon to affect the immune system. In this study, we investigated the effects of diazinon on mast cell functions, such as degranulation and cytokine production.
We used rat basophilic leukemia (RBL)-2H3 cells. To investigate mast cell degranulation, cells were stimulated with A23187 or IgE cross-linking and analyzed beta-hexosaminidase release in supernatants. To investigate the effect of diazinon on late-phase reaction, we tested the gene expression of proinflammatory cytokines such as TNF-alpha. We assessed intracellular calcium mobilization by using Fluo4-AM.
Our results demonstrated that diazinon inhibited mast cell degranulation induced by A23187 or IgE cross-linking in RBL-2H3 cells. Diazinon also inhibited the expression of TNF-alpha induced by A23187- or IgE cross-linking. Furthermore, diazinon did not inhibit calcium mobilization stimulated by A23187.
These results suggested that diazinon mediated anti-allergic effects and the mechanisms for inhibitory action by diazinon might be involved in signaling events after calcium mobilization associated with mast cell activation.
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