STAT3 Activates the Pentraxin 3 Gene in Chronic Lymphocytic Leukemia Cells.
Journal
Journal of immunology (Baltimore, Md. : 1950)
ISSN: 1550-6606
Titre abrégé: J Immunol
Pays: United States
ID NLM: 2985117R
Informations de publication
Date de publication:
15 06 2022
15 06 2022
Historique:
received:
22
11
2021
accepted:
03
04
2022
pubmed:
21
5
2022
medline:
27
7
2022
entrez:
20
5
2022
Statut:
ppublish
Résumé
Pentraxin-related protein 3 (PTX3), commonly produced by myeloid and endothelial cells, is a humoral pattern recognition protein of the innate immune system. Because PTX3 plasma levels of patients with chronic lymphocytic leukemia (CLL) are high and most circulating cells in patients with CLL are CLL cells, we reasoned that CLL cells produce PTX3. Western immunoblotting revealed that low-density cells from seven of seven patients with CLL produce high levels of PTX3, flow cytometry analysis revealed that the PTX3-producing cells are B lymphocytes coexpressing CD19 and CD5, and confocal microscopy showed that PTX3 is present in the cytoplasm of CLL cells. Because STAT3 is constitutively activated in CLL cells, and because we identified putative STAT3 binding sites within the PTX3 gene promoter, we postulated that phosphorylated STAT3 triggers transcriptional activation of PTX3. Immunoprecipitation analysis of CLL cells' chromatin fragments showed that STAT3 Abs precipitated PTX3 DNA. STAT3 knockdown induced a marked reduction in PTX3 expression, indicating a STAT3-induced transcriptional activation of the PTX3 gene in CLL cells. Using an EMSA, we established and used a dual-reporter luciferase assay to confirm that STAT3 binds the PTX3 gene promoter. Downregulation of PTX3 enhanced apoptosis of CLL cells, suggesting that inhibition of PTX3 might benefit patients with CLL.
Identifiants
pubmed: 35595309
pii: jimmunol.2101105
doi: 10.4049/jimmunol.2101105
pmc: PMC9308680
mid: NIHMS1796867
doi:
Substances chimiques
STAT3 Transcription Factor
0
STAT3 protein, human
0
Serum Amyloid P-Component
0
PTX3 protein
148591-49-5
C-Reactive Protein
9007-41-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2847-2855Subventions
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Informations de copyright
Copyright © 2022 by The American Association of Immunologists, Inc.
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