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TNF-alpha-induced growth suppression of CD34+ myeloid leukemic cell lines signals through TNF receptor type I and is associated with NF-kappa B activation.
J Immunol. 1999 Sep 15; 163(6):3106-15.JI

Abstract

Conflicting results have been reported regarding the effect of TNF-alpha on the growth of human primitive hemopoietic cells. In this study, we have examined the effect of TNF-alpha on the proliferation of several CD34+/CD38+ (KG-1, TF-1) and CD34+/CD38- (KG-1a, TF-1a) myeloid leukemic progenitor cell lines. Our data show that TNF-alpha markedly inhibits the growth of these cells in both liquid and soft agar cultures. Addition of GM-CSF or IL-3 does not prevent TNF-alpha-induced growth inhibition. Flow cytometry analyses of propidium iodide-stained cells demonstrated cell death of all four cell lines, as judged by the presence of cells with hypodiploid DNA content after exposure of cells to TNF-alpha for 4 days. Annexin V assays detected apoptosis in TF-1, but not in TF-1a, KG-1, and KG-1a cells in terms of translocation of phosphatidylserine shortly after TNF-alpha treatment. Neutralizing anti-TNF receptor type I (TNFR-I; p55) Ab almost completely reversed TNF-alpha-induced growth inhibition in both liquid and soft agar cultures, whereas anti-TNFR-II (p75) Ab had only a marginal effect. TNF-alpha rapidly induced marked activation of nuclear transcription factor NF-kappa B in all 4 cell lines. The majority of this effect was abolished by the type I receptor Ab, whereas the type II receptor neutralizing Ab had no effect. Our data also show that TNF-alpha is incapable of inducing activation of the mitogen-activated protein kinase pathway in these leukemic cell lines.

Authors+Show Affiliations

Division of Medical Oncology and Hematology, Department of Internal Medicine, University South Florida, Tampa 33612, USA. hu@moffitt.usf.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10477576

Citation

Hu, X, et al. "TNF-alpha-induced Growth Suppression of CD34+ Myeloid Leukemic Cell Lines Signals Through TNF Receptor Type I and Is Associated With NF-kappa B Activation." Journal of Immunology (Baltimore, Md. : 1950), vol. 163, no. 6, 1999, pp. 3106-15.
Hu X, Tang M, Fisher AB, et al. TNF-alpha-induced growth suppression of CD34+ myeloid leukemic cell lines signals through TNF receptor type I and is associated with NF-kappa B activation. J Immunol. 1999;163(6):3106-15.
Hu, X., Tang, M., Fisher, A. B., Olashaw, N., & Zuckerman, K. S. (1999). TNF-alpha-induced growth suppression of CD34+ myeloid leukemic cell lines signals through TNF receptor type I and is associated with NF-kappa B activation. Journal of Immunology (Baltimore, Md. : 1950), 163(6), 3106-15.
Hu X, et al. TNF-alpha-induced Growth Suppression of CD34+ Myeloid Leukemic Cell Lines Signals Through TNF Receptor Type I and Is Associated With NF-kappa B Activation. J Immunol. 1999 Sep 15;163(6):3106-15. PubMed PMID: 10477576.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TNF-alpha-induced growth suppression of CD34+ myeloid leukemic cell lines signals through TNF receptor type I and is associated with NF-kappa B activation. AU - Hu,X, AU - Tang,M, AU - Fisher,A B, AU - Olashaw,N, AU - Zuckerman,K S, PY - 1999/9/8/pubmed PY - 1999/9/8/medline PY - 1999/9/8/entrez SP - 3106 EP - 15 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 163 IS - 6 N2 - Conflicting results have been reported regarding the effect of TNF-alpha on the growth of human primitive hemopoietic cells. In this study, we have examined the effect of TNF-alpha on the proliferation of several CD34+/CD38+ (KG-1, TF-1) and CD34+/CD38- (KG-1a, TF-1a) myeloid leukemic progenitor cell lines. Our data show that TNF-alpha markedly inhibits the growth of these cells in both liquid and soft agar cultures. Addition of GM-CSF or IL-3 does not prevent TNF-alpha-induced growth inhibition. Flow cytometry analyses of propidium iodide-stained cells demonstrated cell death of all four cell lines, as judged by the presence of cells with hypodiploid DNA content after exposure of cells to TNF-alpha for 4 days. Annexin V assays detected apoptosis in TF-1, but not in TF-1a, KG-1, and KG-1a cells in terms of translocation of phosphatidylserine shortly after TNF-alpha treatment. Neutralizing anti-TNF receptor type I (TNFR-I; p55) Ab almost completely reversed TNF-alpha-induced growth inhibition in both liquid and soft agar cultures, whereas anti-TNFR-II (p75) Ab had only a marginal effect. TNF-alpha rapidly induced marked activation of nuclear transcription factor NF-kappa B in all 4 cell lines. The majority of this effect was abolished by the type I receptor Ab, whereas the type II receptor neutralizing Ab had no effect. Our data also show that TNF-alpha is incapable of inducing activation of the mitogen-activated protein kinase pathway in these leukemic cell lines. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/10477576/TNF_alpha_induced_growth_suppression_of_CD34+_myeloid_leukemic_cell_lines_signals_through_TNF_receptor_type_I_and_is_associated_with_NF_kappa_B_activation_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=10477576 DB - PRIME DP - Unbound Medicine ER -