CD45-induced Tumor Necrosis Factor α Production in Monocytes Is Phosphatidylinositol 3-Kinase-dependent and Nuclear Factor-κB-independent

Hayes, A. Louise; Smith, Clive; Foxwell, Brian M.J.; Brennan, Fionula M.

doi:10.1074/jbc.274.47.33455

Cited by 44NF-κB Signaling PathwaysRheumatoid Arthritis Research and TherapiesImmune Response and Inflammation

CD45-induced Tumor Necrosis Factor α Production in Monocytes Is Phosphatidylinositol 3-Kinase-dependent and Nuclear Factor-κB-independent

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Hayes, A. Louise, Smith, Clive, Foxwell, Brian M.J., Brennan, Fionula M.·1999·Journal of Biological Chemistry

DOI 10.1074/jbc.274.47.33455

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Abstract

The pro-inflammatory cytokine tumor necrosis factor (TNF)-alpha plays a pivotal role in the pathogenesis of rheumatoid arthritis. The mechanisms involved in regulating monocyte/macrophage TNFalpha production are not yet fully understood but are thought to involve both soluble factors and cell/cell contact with other cell types. Ligation of certain cell surface receptors, namely CD45, CD44, and CD58, can induce the production of TNFalpha in monocytes. In this paper, we investigate further the signaling pathways utilized by cell surface receptors (specifically CD45) to induce monocyte TNFalpha and compare the common/unique pathways involved with that of lipopolysaccharide. The results indicate that monocyte TNFalpha induced upon CD45 ligation or lipopolysaccharide stimulation is differentially modulated by phosphatidylinositol 3-kinase and nuclear factor-kappaB but similarly regulated by p38 mitogen-activated protein kinase. These results demonstrate that both common and unique signaling pathways are utilized by different stimuli for the induction of TNFalpha. These observations may have a major bearing on approaches to inhibiting TNFalpha production in disease where the cytokine has a pathogenic role.

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CD45 activation can induce the production of TNFα, which in turn activates a family of cell-surface receptors that can mediate cell death.
“Interestingly, CD45 activation can induce the production of TNFα [24] which in turn activates a family of cell-surface receptors that can mediate cell death.”
From Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs (2009) · cites this paper as [24]

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Phosphatidylinositol 5-phosphate 4-kinase γ (PI5P4Kγ), a lipid signalling enigma
Giudici, M.-L., Clarke, J. H., & Irvine, R. F. (2015) · Advances in Biological Regulation · doi:10.1016/j.jbior.2015.11.007 · Cited by 11 · see citing works

Authors: Hayes, A. L., Smith, C., Foxwell, B. M. J., & Brennan, F. M.
Affiliations: Kennedy Institute of Rheumatology (GB)
Corresponding author: Brennan, Fionula M.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1999-11
Volume: 274
Issue: 47
Pages: 33455-33461
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.274.47.33455
OpenAlex: W2123816477
Cited by: 44
References: 71
Citations by year: 2026: 1 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 1
FWCI: 2.34
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 7669 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: Israel Cancer Research Fund
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: CD45, TNF-α, monocytes, phosphatidylinositol 3-kinase, NF-κB, p38 MAPK, lipopolysaccharide, cell surface receptor signaling, rheumatoid arthritis, anti-TNF therapy, CD44, CD58
MeSH terms: Phosphoinositide-3 Kinase Inhibitors, Cells, Cultured, Enzyme Activation, Humans, Monocytes, Tumor Necrosis Factor-alpha, Signal Transduction, NF-kappa B, Leukocyte Common Antigens, Phosphatidylinositol 3-Kinases, Ribosomal Protein S6 Kinases, Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases

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CD45-induced Tumor Necrosis Factor α Production in Monocytes Is Phosphatidylinositol 3-Kinase-dependent and Nuclear Factor-κB-independent

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