The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Inhibition of NF-κB Activation by Pyrrolidine Dithiocarbamate Prevents In Vivo Expression of Proinflammatory Genes
Abstract
Background—The inability to inhibit multiple mediators of septic shock represents a major hurdle in the treatment of septic shock. In vivo inhibition of nuclear factor (NF)-κB activation, a transcription factor regulating expression of many proinflammatory genes, could provide a useful strategy for the treatment of septic shock. Methods and Results—In rats challenged with lipopolysaccharide (LPS) 8 mg/kg IV, we determined the time course of NF-κB activation and expression of multiple inflammatory signals: tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), cytokine-inducible neutrophil chemoattractant (CINC), and intercellular adhesion molecule-1 (ICAM)-1. We studied the effects of in vivo inhibition of NF-κB activation using pyrrolidine dithiocarbamate (PDTC) on the expression of these mediators. NF-κB activation preceded the induction of TNF-α, COX-2, CINC, and ICAM-1 mRNAs. PDTC prevented the LPS-induced NF-κB activation but did not inhibit activation of the transcription factors AP-1, Sp-1, and CREB. PDTC inhibited the LPS-induced expression of TNF-α, COX-2, CINC, and ICAM-1 mRNA and proteins and reduced the LPS-induced increases in plasma TNF-α, 6-keto-prostaglandin F 1α, and CINC concentrations. Inhibition of expression of these mediators prevented the increases in myeloperoxidase activity (a measure of neutrophil sequestration) in the heart, lungs, and liver. Conclusions—NF-κB activation correlates with LPS-induced expression of TNF-α, COX-2, CINC, and ICAM-1 genes in vivo. PDTC inhibits NF-κB activation and expression of these proinflammatory genes and their products. Thus, blocking NF-κB activation may be an effective strategy in the treatment of septic shock.
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Cites
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Pathogenetic Mechanisms of Septic Shock
Epstein, F. H., & Parrillo, J. E. (1993) · New England Journal of Medicine · doi:10.1056/nejm199305203282008 · Cited by 1,548
Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells.
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Cloning Two Isoforms of Rat Cyclooxygenase: Differential Regulation of Their Expression
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Nonsteroidal anti‐inflammatory drugs prevent early diabetic retinopathy via TNF‐α suppression
M. Joussen, A., Poulaki, V., Mitsiades, N., Kirchhof, B., Koizumi, K., Döhmen, S., & P. Adamis, A. (2002) · The FASEB Journal · doi:10.1096/fj.01-0707fje · Cited by 567
Oxidative stress and gene expression in sepsis
Macdonald, J., Galley, H. F., & Webster, N. R. (2003) · British Journal of Anaesthesia · doi:10.1093/bja/aeg034 · Cited by 497
Immune cells: free radicals and antioxidants in sepsis
Victor, V. M., Rocha, M., & De la Fuente, M. (2004) · International Immunopharmacology · doi:10.1016/j.intimp.2004.01.020 · Cited by 310
Parodi, F. E., Mao, D., Ennis, T. L., Bartoli, M. A., & Thompson, R. W. (2005) · Journal of Vascular Surgery · doi:10.1016/j.jvs.2004.12.030 · Cited by 65
Hong, Y.-H., Kao, C., Chang, C.-C., Chang, F.-K., Song, T.-Y., Houng, J.-Y., & Wu, C.-H. (2023) · Agriculture · doi:10.3390/agriculture13020451 · Cited by 15
Metadata
- Authors
- Liu, S. F., Ye, X., & Malik, A. B.
- Venue
- Circulation
- Published
- 1999-09-21
- Volume
- 100
- Issue
- 12
- Pages
- 1330-1337
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2131924126
- Cited by
- 346
- References
- 28
- FWCI
- 6.52
- Type
- journal article
- Language
- en
- Open access
- closed
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