Pyrrolidine dithiocarbamate-induced macrophage inflammatory protein-2 gene expression is NF-κB-independent but c-Jun-dependent in macrophage cell line RAW 264.7
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- Pyrrolidine dithiocarbamate-induced macrophage inflammatory protein-2 gene expression is NF-κB-independent but c-Jun-dependent in macrophage cell line RAW 264.7
- W J Sohn; K W Lee; Y Lee; J H Han; Yong Kyung Choe; D S Kim; H J Kwon
- Bibliographic Citation
- Molecular Immunology, vol. 42, no. 10, pp. 1165-1175
- Publication Year
- Pyrrolidine dithiocarbamate (PDTC) is a stable compound that acts as antioxidant or prooxidant, and is widely used to inhibit the activation of NF-κB. PDTC was also reported to activate NF-κB depending on its dose and metal ions in PC12 cells. In this work, we demonstrated a working mechanism of PDTC and its effects on the proinflammatory cytokine gene expression in a mouse macrophage cell line, RAW 264.7. PDTC alone induced NF-κB-independent MIP-2 promoter activation that can be assessed by transient transfection and confocal image analysis. The involvement of AP-1 transcription factor was noticed by promoter deletion/site-specific mutation analysis and electrophoretic mobility shift assay (EMSA). Among three different mitogen-activated protein kinase (MAPK) pathways tested, only the stress-activated protein kinase (SAPK)/Jun N-terminal kinase (JNK) pathway was significantly activated in RAW 264.7 cells after the stimulation with PDTC. Using pathway-specific inhibitors, we found that the SAPK/JNK pathway is clearly associated with PDTC-induced MIP-2 gene expression. Our experimental results indicate that PDTC-induced proinflammatory cytokine expressions are mediated by SAPK/JNK pathway, which activates AP-1.
- AP-1macrophagesMIP-2PDTCproinflammatory cytokine
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