Suppression of IL-2 and IL-4 gene expression by nodularin through the reduced NF-AT binding activity

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Suppression of IL-2 and IL-4 gene expression by nodularin through the reduced NF-AT binding activity
Sung Su Yea; Hwan Mook Kim; Jeon Young Jin; Hee Moak Oh; Hye Gwang Jeong; Kyu-Hwan Yang
Bibliographic Citation
Toxicology Letters, vol. 114, no. 1-3, pp. 215-224
Publication Year
Nodularin is a cyclic peptide produced by cyanobacteria. In the present study, the inhibitory effect of nodularin on T lymphocyte functions was demonstrated. Direct addition of nodularin to B6C3F1 mouse splenocyte cultures produced a concentration-dependent inhibition of the lymphoproliferative response to concanavalin A stimulation. Nodularin inhibited PMA plus ionomycin (Io)-induced IL-2 mRNA expression in murine splenocytes and thymocytes as determined by quantitative/competitive RT-PCR. To further characterize the mechanism for the transcriptional regulation of IL-2, the binding activity of transcription factors, NF-AT, AP-1, NF-κB, and Oct, was evaluated by electrophoretic mobility shift assays in mouse splenocytes. Nodularin reduced the NF-AT binding activity in PMA/Io-induced splenocytes, but no significant effect was observed on AP-1, NF-κB, or Oct binding activity. Nodularin also inhibited IL-4 mRNA expression in PMA/Io-stimulated murine splenocytes. These results suggest that T lymphocyte is a possible cellular target of nodularin, and the inhibitory effect of nodularin on T-cell specific transcription factor NF-AT induces T-cell dysfunction, which leads to a diminution in IL-2 and IL-4 gene transcription.
T lymphocytesInterleukin-2Interleukin-4NF-ATNodularin
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Synthetic Biology and Bioengineering Research Institute > Cell Factory Research Center > 1. Journal Articles
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