Growth Hormone, Insulin-like Growth Factor I, and Immune Function

Kelley, Keith W.; Arkins, Seán; Li, Y. M.; Biragyn, Arya

doi:10.1007/978-3-642-78217-6_16

Cited by 4 publications

(1 citation statement)

References 88 publications

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“…There is substantial evi dence that IGF-1 causes many of the same effects as growth hormone on leukocytes [reviewed in ref. 37,38], Progeni tors of T lymphocytes [50] and myeloid cells [36, 51.52], as well as activated human T lymphocytes [53], monocytes [54] and alveolar macrophages from patients with intersti tial lung disease [55], express specific receptors for IGF-1. However, it is largely unknown whether growth hormone acts directly on leukocytes to modulate immune evenls or if it acts indirectly by inducing the endocrine, paracrine or autocrine synthesis of IGF-1.…”

Section: Growth Hormone and Igf-1 Act On Hematopoietic Cellsmentioning

confidence: 99%

Growth Hormone, Growth Factors and Hematopoiesis

et al. 1996

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Hypocellularity of primary lymphoid organs is a distinctive and reproducible characteristic of aged humans and animals. Similar changes have been reported in both hypophysectomized and dwarf rodents. In the bone marrow of these animals, there is an associated reduction in the number of erythroid, lymphoid and myeloid elements. Implantation of growth hormone (GH)-secreting GH₃ pituitary cells or infusion of growth hormone into aged rodents dramatically improves cellularity of both the thymus gland and bone marrow. At present it is unknown whether these effects are due to direct effects of growth hormone on hematopoietic cells or if they are caused by the induction of insulin-like growth factor-1 (IGF-1) synthesis. We recently discovered that colony-stimulating factor-1 (CSF-1) and interleukin-3 (IL-3) induce expression and synthesis of the IGF-1 peptide in murine bone marrow cells. Transcripts for IGF-1 increase approximately 50-fold during differentiation over the negligible levels that are expressed in freshly isolated bone marrow cells. Two potential functions of macrophage-derived IGF-1 are to: (a) increase the proliferation of early or committed bone marrow progenitors and (b) reduce their rate of cell death. In support of the first possibility, IGF binding protein-3 significantly inhibits the proliferation of CSF-1-treated bone marrow cells and this inhibition can be reversed by addition of exogenous IGF-1. In support of the second possibility, we have induced apoptosis of both nonadherent bone marrow cells and a myeloid progenitor cell line by depriving these cells of CSFs. Preliminary results indicate that addition of IGF-1 to these cells reduces apoptotic cell death by 50%. These data establish that two different CSFs, CSF-1 and IL-3, induce abundant expression of IGF-1 as these cells differentiate into more mature hematopoietic cells. This model offers a novel approach for investigating the developmental expression of IGF-1 during defined differentiation pathways of hematopoietic cells. If IGF-1 is indeed proven to act as a survival factor for hematopoietic progenitors, these data would support the idea that the hypocellularity of primary lymphoid tissues in aged animals is related to the limited availability to these cells of either growth hormone or IGF-1.

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Section: Growth Hormone and Igf-1 Act On Hematopoietic Cellsmentioning

confidence: 99%

Growth Hormone, Growth Factors and Hematopoiesis

et al. 1996

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Immune parameters in growing pigs given growth hormone-releasing factor (GRF) continuously or intermittently

Brousseau

Dumais

Krzystyniak

et al. 1997

Livestock Production Science

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Influence of IGF-I and Cell Density on MDR1 Expression in the T-Lymphoblastoid Cell Line CCRF-CEM

et al. 1999

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The debate about a direct or indirect effect of GH and IGF-I on the recurrence of malignancy, especially in the case of rhGH therapy in patients with leukemia, is still going on. Recent studies suggested that IGF-I plays a role in drug resistance during anticancer therapy. This resistance to diverse cytotoxic drugs, named multidrug-resistance (MDR), is mainly due to high levels of P-glycoprotein (P-gp). The gene encoding this membrane-associated transporter protein was named MDR1, and increased levels of P-gp are linked to enhanced MDR1 mRNA expression. Our aim was to investigate a possible effect of rhIGF-I on MDR1 gene expression in vitro. We cultured the T-lymphoblastoid cell line CCRF-CEM with different rhIGF-I concentrations (0, 5, 20 and 50 ng/ml) in serum-free medium for 3 days. CCRF-CEM cells are drug-sensitive and express MDR1 at low levels. MDR1 mRNA expression was measured by semiquantitative RT-PCR using a competitive assay with a heterologous DNA construct. In addition, GAPDH mRNA was amplified as an internal control for RNA integrity. P-gp activity was determined by a flow cytometric assay measuring rhodamine 123 accumulation. Furthermore, cell proliferation was monitored in all experiments. Our data do not support an effect of rhIGF-I on MDR1 mRNA expression, P-gp activity or cell proliferation in the CCRF-CEM cell line. MDR1 mRNA levels were inversely correlated to cell density with high significance (p < 0.0001). In conclusion, multidrug resistance linked to P-gp is not induced by IGF-I in CCRF-CEM cells. At high density, CCRF-CEM cells downregulate MDR1 gene expression. Our experimental model provides a very useful tool for monitoring the influence of growth factors on multidrug resistance in vitro.

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Growth Hormone, Insulin-like Growth Factor I, and Immune Function

Cited by 4 publications

References 88 publications

Growth Hormone, Growth Factors and Hematopoiesis

Growth Hormone, Growth Factors and Hematopoiesis

Immune parameters in growing pigs given growth hormone-releasing factor (GRF) continuously or intermittently

Influence of IGF-I and Cell Density on MDR1 Expression in the T-Lymphoblastoid Cell Line CCRF-CEM

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