Tumor necrosis factor alpha inhibits insulin-like growth factor I-induced hematopoietic cell survival and proliferation.
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.
Shen
Wen Hong
WH
University of Illinois, Laboratory of Immunophysiology, Department of Animal Sciences, 207 Edward R. Madigan Laboratory, 1201 West Gregory Drive, Urbana, Illinois 61801, USA.
Zhou
Jian-Hua
JH
Broussard
Suzanne R
SR
Johnson
Rodney W
RW
Dantzer
Robert
R
Kelley
Keith W
KW
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004347:Drug Interactions; D018922:HL-60 Cells; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000970:Antineoplastic Agents; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I; D004247:DNA