Tumor necrosis factor alpha inhibits insulin-like growth factor I-induced hematopoietic cell survival and proliferation. Academic Article uri icon

Overview

abstract

  • Proinflammatory cytokines, such as TNFalpha and IL-1beta, are both cytostatic and cytotoxic. In contrast, IGF-I promotes proliferation and survival of hematopoietic progenitor cells. In this report, we establish that both the cytostatic and cytotoxic activity of TNFalpha on murine myeloid progenitor cells is only evident in the presence of IGF-I. We first confirmed that IGF-I (100 ng/ml) increases DNA synthesis and reduces apoptosis in murine myeloid progenitor cells induced to die by growth factor withdrawal. TNFalpha inhibits, in a dose-dependent fashion from 0.1 to 10 ng/ml, both activities of IGF-I. TNFalpha activity was not detected in the absence of IGF-I. Another proinflammatory cytokine, IL-1beta, did not inhibit IGF-I-induced activity in murine factor-dependent cell progenitor-1/Mac-1 cells. However, the ability of TNFalpha to impair IGF-I-induced DNA synthesis in human promyeloid cells extends to IL-1beta. Statistically significant inhibition of all these events occurs at very low concentrations of 1 ng/ml or less. These results support the general concept that proinflammatory cytokines impair the actions of hormones on hematopoietic cells, leading to IGF-I receptor resistance.

publication date

  • April 15, 2004

Research

keywords

  • Antineoplastic Agents
  • Hematopoietic Stem Cells
  • Insulin-Like Growth Factor I
  • Tumor Necrosis Factor-alpha

Identity

Scopus Document Identifier

  • 3042634459

Digital Object Identifier (DOI)

  • 10.1210/en.2004-0246

PubMed ID

  • 15087433

Additional Document Info

volume

  • 145

issue

  • 7