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Pyrrolidine dithiocarbamate-induced macrophage inflammatory protein-2 gene expression is NF-kappaB-independent but c-Jun-dependent in macrophage cell line RAW 264.7.
Mol Immunol. 2005 Jun; 42(10):1165-75.MI

Abstract

Pyrrolidine dithiocarbamate (PDTC) is a stable compound that acts as antioxidant or prooxidant, and is widely used to inhibit the activation of NF-kappaB. PDTC was also reported to activate NF-kappaB 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-kappaB-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.

Authors+Show Affiliations

Institute of Life Science and Biotechnology, College of Science, Yonsei University, 134 Shinchon-Dong, Seodaemoon-Gu, Seoul 120-749, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15829306

Citation

Sohn, Wern-Joo, et al. "Pyrrolidine Dithiocarbamate-induced Macrophage Inflammatory Protein-2 Gene Expression Is NF-kappaB-independent but c-Jun-dependent in Macrophage Cell Line RAW 264.7." Molecular Immunology, vol. 42, no. 10, 2005, pp. 1165-75.
Sohn WJ, Lee KW, Lee Y, et al. Pyrrolidine dithiocarbamate-induced macrophage inflammatory protein-2 gene expression is NF-kappaB-independent but c-Jun-dependent in macrophage cell line RAW 264.7. Mol Immunol. 2005;42(10):1165-75.
Sohn, W. J., Lee, K. W., Lee, Y., Han, J. H., Choe, Y. K., Kim, D. S., & Kwon, H. J. (2005). Pyrrolidine dithiocarbamate-induced macrophage inflammatory protein-2 gene expression is NF-kappaB-independent but c-Jun-dependent in macrophage cell line RAW 264.7. Molecular Immunology, 42(10), 1165-75.
Sohn WJ, et al. Pyrrolidine Dithiocarbamate-induced Macrophage Inflammatory Protein-2 Gene Expression Is NF-kappaB-independent but c-Jun-dependent in Macrophage Cell Line RAW 264.7. Mol Immunol. 2005;42(10):1165-75. PubMed PMID: 15829306.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pyrrolidine dithiocarbamate-induced macrophage inflammatory protein-2 gene expression is NF-kappaB-independent but c-Jun-dependent in macrophage cell line RAW 264.7. AU - Sohn,Wern-Joo, AU - Lee,Keun-Wook, AU - Lee,Younghee, AU - Han,Jung Ho, AU - Choe,Yong-Kyoung, AU - Kim,Doo-Sik, AU - Kwon,Hyung-Joo, Y1 - 2005/01/07/ PY - 2004/09/10/received PY - 2005/4/15/pubmed PY - 2005/7/19/medline PY - 2005/4/15/entrez SP - 1165 EP - 75 JF - Molecular immunology JO - Mol Immunol VL - 42 IS - 10 N2 - Pyrrolidine dithiocarbamate (PDTC) is a stable compound that acts as antioxidant or prooxidant, and is widely used to inhibit the activation of NF-kappaB. PDTC was also reported to activate NF-kappaB 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-kappaB-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. SN - 0161-5890 UR - https://www.unboundmedicine.com/medline/citation/15829306/Pyrrolidine_dithiocarbamate_induced_macrophage_inflammatory_protein_2_gene_expression_is_NF_kappaB_independent_but_c_Jun_dependent_in_macrophage_cell_line_RAW_264_7_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-5890(04)00472-9 DB - PRIME DP - Unbound Medicine ER -