Cited by 84Inflammatory mediators and NSAID effectsSignaling Pathways in DiseaseNF-κB Signaling Pathways

Nonsteroidal anti-inflammatory drugs suppress T-cell activation by inhibiting p38 MAPK induction

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Paccani, Silvia Rossi, Boncristiano, Marianna, Ulivieri, Cristina, D'Elios, Mario Milco, Del Prete, Gianfranco, Baldari, Cosima T.·2002·Journal of Biological Chemistry

Abstract

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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  1. Fujishima, H., Sanchez Mejia, R. O., Bingham, C. O., Lam, B. K., Sapirstein, A., Bonventre, J. V., Austen, K. F., and Arm, J. P. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 4803-4807

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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
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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