Nonsteroidal anti-inflammatory drugs suppress T-cell activation by inhibiting p38 MAPK induction
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In addition to antagonizing inflammation by inhibiting the activity of cyclooxygenases (COX), nonsteroidal anti-inflammatory drugs (NSAID) block T-cell activation. The immunosuppressant activity of NSAID correlates with their ability to block transcription factors required for the expression of inducible response genes triggered by T-cell antigen receptor (TCR) engagement. Whereas the inhibition of nuclear factor-kappaB by aspirin and sodium salicylate can be partly accounted for by their binding to IkappaB kinase-beta, the broad range of transcriptional targets of NSAID suggests that the products of COX activity might affect one or more among the early steps in the TCR-signaling cascade. Here we show that the inhibition of NF-AT activation by NSAID correlates with a selective inhibition of p38 MAP kinase induction. The suppression of TCR-dependent p38 activation by NSAID can be fully overcome by prostaglandin E(2), underlining the requirement for COX activity in p38 activation. Furthermore, the inhibition of COX-1 results in defective induction of the COX-2 gene, which behaves as an early TCR responsive gene. The data identify COX-1 and COX-2 as integral and sequential components of TCR signaling to p38 and contribute to elucidate the molecular basis of immunosuppression by NSAID.
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Ibuprofen and other nonsteroidal anti-inflammatory drugs inhibit p38 MAPK activity in Jurkat T cells.
“ibuprofen and other nonsteroidal anti-inflammatory drugs have been shown to inhibit p38 MAPK activity in Jurkat T cells,72,73”
From Cytokines and Glucocorticoid Receptor Signaling (2009) · cites this paper as [72]
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- Authors
- Paccani, S. R., Boncristiano, M., Ulivieri, C., D'Elios, M. M., Del Prete, G., & Baldari, C. T.
- Affiliations
- University of Siena (IT)
- Corresponding author
- Baldari, Cosima T.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-01
- Volume
- 277
- Issue
- 2
- Pages
- 1509-1513
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2108237688
- Cited by
- 84
- References
- 29
- Citations by year
- 2026: 2 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 6 · 2018: 3 · 2017: 3 · 2016: 2 · 2015: 2 · 2014: 4 · 2013: 3 · 2012: 1
- FWCI
- 4.71
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Use Siena air (University of Siena) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- nonsteroidal anti-inflammatory drugs, T cell activation, p38 MAPK, cyclooxygenase, cyclooxygenase-1, cyclooxygenase-2, T cell receptor signaling, NFAT, immunosuppression, prostaglandin E2, aspirin, salicylates, IκB kinase β
- MeSH terms
- Anti-Inflammatory Agents, Non-Steroidal, Cell Line, DNA-Binding Proteins, Enzyme Activation, Enzyme Induction, Humans, Isoenzymes, Lymphocyte Activation, Membrane Proteins, Nuclear Proteins, Prostaglandin-Endoperoxide Synthases, Recombinant Fusion Proteins, T-Lymphocytes, Transcription Factors, Genes, Reporter, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, p38 Mitogen-Activated Protein Kinases, NFATC Transcription Factors, Cyclooxygenase 1, Cyclooxygenase 2
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