Combinations of ERK and p38 MAPK inhibitors ablate tumor necrosis factor-alpha (TNF-alpha ) mRNA induction. Evidence for selective destabilization of TNF-alpha transcripts - PubMed (original) (raw)
. 2001 Mar 2;276(9):6666-74.
doi: 10.1074/jbc.M005486200. Epub 2000 Nov 13.
Affiliations
- PMID: 11076936
- DOI: 10.1074/jbc.M005486200
Free article
Combinations of ERK and p38 MAPK inhibitors ablate tumor necrosis factor-alpha (TNF-alpha ) mRNA induction. Evidence for selective destabilization of TNF-alpha transcripts
K Rutault et al. J Biol Chem. 2001.
Free article
Abstract
Tumor necrosis factor-alpha (TNF-alpha) is a potent proinflammatory cytokine whose synthesis and secretion are implicated in diverse pathologies. Hence, inhibition of TNF-alpha transcription or translation and neutralization of its protein product represent major pharmaceutical strategies to control inflammation. We have studied the role of ERK and p38 mitogen-activated protein (MAP) kinase in controlling TNF-alpha mRNA levels in differentiated THP-1 cells and in freshly purified human monocytes. We show here that it is possible to produce virtually complete inhibition of lipopolysaccharide-stimulated TNF-alpha mRNA accumulation by using a combination of ERK and p38 MAP kinase inhibitors. Furthermore, substantial inhibition is achievable using combinations of 1 microm of each inhibitor, whereas inhibitors used individually are incapable of producing complete inhibition even at high concentrations. Finally, addressing mechanisms involved, we show that inhibition of p38 MAP kinase selectively destabilizes TNF-alpha transcripts but does not affect degradation of c-jun transcripts. These results impinge on the controversy in the literature surrounding the mode of action of MAP kinase inhibitors on TNF-alpha mRNA and suggest the use of combinations of MAP kinase inhibitors as an effective anti-inflammatory strategy.
Similar articles
- Different mitogen-activated protein kinase signaling pathways cooperate to regulate tumor necrosis factor alpha gene expression in T lymphocytes.
Hoffmeyer A, Grosse-Wilde A, Flory E, Neufeld B, Kunz M, Rapp UR, Ludwig S. Hoffmeyer A, et al. J Biol Chem. 1999 Feb 12;274(7):4319-27. doi: 10.1074/jbc.274.7.4319. J Biol Chem. 1999. PMID: 9933633 - A critical role for p38 mitogen-activated protein kinase in the maturation of human blood-derived dendritic cells induced by lipopolysaccharide, TNF-alpha, and contact sensitizers.
Arrighi JF, Rebsamen M, Rousset F, Kindler V, Hauser C. Arrighi JF, et al. J Immunol. 2001 Mar 15;166(6):3837-45. doi: 10.4049/jimmunol.166.6.3837. J Immunol. 2001. PMID: 11238627 - Activation of mitogen-activated protein kinase p38 and extracellular signal-regulated kinase is involved in glass fiber-induced tumor necrosis factor-alpha production in macrophages.
Ye J, Zeidler P, Young SH, Martinez A, Robinson VA, Jones W, Baron P, Shi X, Castranova V. Ye J, et al. J Biol Chem. 2001 Feb 16;276(7):5360-7. doi: 10.1074/jbc.M008814200. Epub 2000 Nov 21. J Biol Chem. 2001. PMID: 11087751 - p38 MAP kinase and MKK-1 co-operate in the generation of GM-CSF from LPS-stimulated human monocytes by an NF-kappa B-independent mechanism.
Meja KK, Seldon PM, Nasuhara Y, Ito K, Barnes PJ, Lindsay MA, Giembycz MA. Meja KK, et al. Br J Pharmacol. 2000 Nov;131(6):1143-53. doi: 10.1038/sj.bjp.0703684. Br J Pharmacol. 2000. PMID: 11082122 Free PMC article.
Cited by
- Personalizing Therapy Outcomes through Mitogen-Activated Protein Kinase Pathway Inhibition in Non-Small Cell Lung Cancer.
Alsharoh H, Chiroi P, Isachesku E, Tanasa RA, Pop OL, Pirlog R, Berindan-Neagoe I. Alsharoh H, et al. Biomedicines. 2024 Jul 5;12(7):1489. doi: 10.3390/biomedicines12071489. Biomedicines. 2024. PMID: 39062063 Free PMC article. Review. - Hypoxia exacerbates intestinal injury and inflammatory response mediated by myeloperoxidase during Salmonella Typhimurium infection in mice.
Zhu Q, Han Y, Wang X, Jia R, Zhang J, Liu M, Zhang W. Zhu Q, et al. Gut Pathog. 2023 Nov 30;15(1):62. doi: 10.1186/s13099-023-00586-5. Gut Pathog. 2023. PMID: 38037141 Free PMC article. - Multiple p38/JNK mitogen-activated protein kinase (MAPK) signaling pathways mediate salt chemotaxis learning in C. elegans.
Huang T, Suzuki K, Kunitomo H, Tomioka M, Iino Y. Huang T, et al. G3 (Bethesda). 2023 Aug 30;13(9):jkad129. doi: 10.1093/g3journal/jkad129. G3 (Bethesda). 2023. PMID: 37310929 Free PMC article. - Differential Effects of Toll-Like Receptor Activation and Differential Mediation by MAP Kinases of Immune Responses in Microglial Cells.
Kwon J, Arsenis C, Suessmilch M, McColl A, Cavanagh J, Morris BJ. Kwon J, et al. Cell Mol Neurobiol. 2022 Nov;42(8):2655-2671. doi: 10.1007/s10571-021-01127-x. Epub 2021 Jul 23. Cell Mol Neurobiol. 2022. PMID: 34297254 Free PMC article. - Assessment of cellular and molecular changes in the rat brain after gamma radiation and radioprotection by anisomycin.
Kočović DM, Bajuk-Bogdanović D, Pećinar I, Nedeljković BB, Daković M, Andjus PR. Kočović DM, et al. J Radiat Res. 2021 Sep 13;62(5):793-803. doi: 10.1093/jrr/rrab045. J Radiat Res. 2021. PMID: 34062561 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous