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Nonsteroidal anti-inflammatory drugs inhibit a Fyn-dependent pathway coupled to Rac and stress kinase activation in TCR signaling
Open accessAbstract
In addition to their anti-inflammatory properties, nonsteroidal anti-inflammatory drugs (NSAIDs) harbor immunosuppressive activities related to their capacity both to inhibit cyclooxygenases (COXs) and to act as peroxisome proliferator-activated receptor (PPAR) ligands. We have previously shown that the stress-activated kinase p38 is a selective target of NSAIDs in T cells. Here we have investigated the effect of NSAIDs on the signaling pathway triggered by the T-cell antigen receptor (TCR) and leading to stress kinase activation. The results show that nonselective and COX-1–selective NSAIDs also block activation of the stress kinase c-Jun N-terminal kinase (JNK) and that prostaglandin-E2 (PGE2) reverses this block and enhances TCR-dependent JNK activation. Analysis of the activation state of the components upstream of p38 and JNK showed that NSAIDs inhibit the serine-threonine kinase p21-activated protein kinase 1 (Pak1) and the small guanosine 5′-triphosphatase (GTPase) Rac, as well as the Rac-specific guanine nucleotide exchanger, Vav. Furthermore, activation of Fyn, which controls Vav phosphorylation, is inhibited by NSAIDs, whereas activation of lymphocyte-specific protein tyrosine kinase (Lck) and of the Lck-dependent tyrosine kinase cascade is unaffected. Accordingly, constitutively active Fyn reverses the NSAID-dependent stress kinase inhibition. The data identify COX-1 as an important early modulator of TCR signaling and highlight a TCR proximal pathway selectively coupling the TCR to stress kinase activation.
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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 [73]
Anisomycin is a potent activator of JNK signaling pathways.
“Recent data also indicate that anisomycin is a potent activator of JNK signaling pathways,73”
From Cytokines and Glucocorticoid Receptor Signaling (2009) · cites this paper as [73]
The section “COX-1 is required for p38 and JNK stress kinase activation” discusses JNK activation following TCR engagement, but does not address anisomycin. Searches for “anisomycin” and the claim’s phrasing found no passage about its effect on JNK; page numbers were not available in our copy. (LLM, conf=0.76)
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References 61 · Cited by 17
Research works printed but not linked: 7
- Wallace JL. Distribution and expression of cyclooxygenase (COX) isoenzymes, their physiological roles, and the categorization of nonsteroidal anti-inflammatory drugs (NSAIDs). Am J Med. 1999;107: 11S-16S. · DOI
- Benard V, Bohl BP, Bokoch GM. Characterization of rac and cdc42 activation in chemoattractant-stimulated human neutrophils using a novel assay for active GTPases. J Biol Chem. 1999;274: 13198-13204. · DOI
- Bustelo XR. Regulatory and signaling properties of the Vav family. Mol Cell Biol. 2000;20: 1461-1477. · DOI
- Zhang S, Han J, Sells MA, et al. Rho family GT-Pases regulate p38 mitogen-activated protein kinase through the downstream mediator Pak1. J Biol Chem. 1995;270: 23934-23936. · DOI
- Valensin S, Rossi Paccani S, Ulivieri C, et al. F-actin dynamics control segregation of the TCR signaling cascade to clustered lipid rafts. Eur J Immunol. 2002;32: 435-446. · DOI
- Cattan N, Mary D, Peleraux A, Mari B, Aussel C, Rossi B. Prostaglandin B(2) delivers a co-stimulatory signal leading to T cell activation. Eur Cytokine Netw. 2000;11: 293-299.
- Bhattacharya M, Peri KG, Almazan G, et al. Nuclear localization of prostaglandin E2 receptors. Proc Natl Acad Sci U S A. 1998;95: 15792-15797. · DOI
Metadata
- Authors
- Paccani, S. R., Patrussi, L., Ulivieri, C., Masferrer, J. L., D'Elios, M. M., & Baldari, C. T.
- Affiliations
- University of Siena (IT)
- From the Department of Evolutionary Biology, University of Siena, Siena, Italy; Oncology Discovery Research, Pfizer Corporation, St Louis, MO; and Department of Internal Medicine and Immunoallergology, University of Florence, Florence, Italy.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2005-03-01
- Volume
- 105
- Issue
- 5
- Pages
- 2042-2048
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1994140458
- Cited by
- 17
- References
- 61
- Citations by year
- 2018: 2 · 2016: 1 · 2015: 1 · 2013: 1
- FWCI
- 0.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion)
- Use Siena air (University of Siena) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- nonsteroidal anti-inflammatory drugs, T cell receptor signaling, Fyn, Rac GTPase, Vav guanine nucleotide exchange factor, PAK1, c-Jun N-terminal kinase, p38 MAPK, cyclooxygenase-1, prostaglandin E2, immunosuppression
- MeSH terms
- Anti-Inflammatory Agents, Non-Steroidal, Humans, Membrane Proteins, Prostaglandin-Endoperoxide Synthases, Proto-Oncogene Proteins, Receptors, Antigen, T-Cell, Dinoprostone, src-Family Kinases, Jurkat Cells, rac GTP-Binding Proteins, MAP Kinase Signaling System, JNK Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases, Proto-Oncogene Proteins c-fyn, Cyclooxygenase 1
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