TY - JOUR
T1 - Tumor necrosis factor α inhibits insulin-like growth factor I-induced hematopoietic cell survival and proliferation
AU - Shen, Wen Hong
AU - Zhou, Jian Hua
AU - Broussard, Suzanne R.
AU - Johnson, Rodney W.
AU - Dantzer, Robert
AU - Kelley, Keith W.
PY - 2004/7
Y1 - 2004/7
N2 - Proinflammatory cytokines, such as TNFα and IL-1β, 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 TNFα 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. TNFα inhibits, in a dose-dependent fashion from 0.1 to 10 ng/ml, both activities of IGF-I. TNFα activity was not detected in the absence of IGF-I. Another proinflammatory cytokine, IL-1β, did not inhibit IGF-I-induced activity in murine factor-dependent cell progenitor-1/Mac-1 cells. However, the ability of TNFα to impair IGF-I-induced DNA synthesis in human promyeloid cells extends to IL-1β. 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.
AB - Proinflammatory cytokines, such as TNFα and IL-1β, 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 TNFα 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. TNFα inhibits, in a dose-dependent fashion from 0.1 to 10 ng/ml, both activities of IGF-I. TNFα activity was not detected in the absence of IGF-I. Another proinflammatory cytokine, IL-1β, did not inhibit IGF-I-induced activity in murine factor-dependent cell progenitor-1/Mac-1 cells. However, the ability of TNFα to impair IGF-I-induced DNA synthesis in human promyeloid cells extends to IL-1β. 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.
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U2 - 10.1210/en.2004-0246
DO - 10.1210/en.2004-0246
M3 - Article
C2 - 15087433
AN - SCOPUS:3042634459
SN - 0013-7227
VL - 145
SP - 3101
EP - 3105
JO - Endocrinology
JF - Endocrinology
IS - 7
ER -