scholarly journals Inhibition by Interleukin-1β and Tumor Necrosis Factor-α of the Insulin-Like Growth Factor I Messenger Ribonucleic Acid Response to Growth Hormone in Rat Hepatocyte Primary Culture*

Endocrinology ◽  
1997 ◽  
Vol 138 (3) ◽  
pp. 1078-1084 ◽  
Author(s):  
Jean-Paul Thissen ◽  
Josiane Verniers
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Mrna Levels ◽  
Factor I ◽  
Tnf Α ◽  
Igf I ◽  
Necrosis Factor ◽  
I Gene

Abstract The cytokines are the putative mediators of the catabolic reaction that accompanies infection and trauma. Evidence suggests that their catabolic actions are indirect and potentially mediated through changes in hormonal axis such as the hypothalamo-pituitary-adrenal axis. Insulin-like growth factor I (IGF-I) is a GH-dependent growth factor that regulates the protein metabolism. To determine whether cytokines can directly inhibit the production of IGF-I by the liver, we investigated the regulation of IGF-I gene expression by interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α (10 ng/ml) in a model of rat primary cultured hepatocytes. Hepatocytes were isolated by liver collagenase perfusion and cultured on Matrigel 48 h before experiments. Each experiment was performed in at least three different animals. In the absence of GH, IL-1β and TNF-α did not affect the IGF-I messenger RNA (mRNA) basal levels, whereas IL-6 increased it by a factor of 2.5 after 24 h (P < 0.05). GH (500 ng/ml) alone stimulated the IGF-I gene expression markedly (5- to 10-fold increase) after 24 h (P < 0.001). IL-1β, and TNF-α to a lesser extent, dramatically inhibited the IGF-I mRNA response to GH (IL-1β: −82%, P < 0.001 and TNF-α: −47%, P < 0.01). The half-maximal inhibition of the IGF-I mRNA response to GH was observed for a concentration of IL-1β between 0.1 and 1 ng/ml. Moreover, IL-1β abolished the IL-6-induced IGF-I mRNA response. In contrast, IL-6 did not impair the IGF-I mRNA response to GH. To determine the potential role of the GH receptor (GHR) and the GH-binding protein (GHBP) in this GH resistance, we assessed the GHR and GHBP mRNAs response to these cytokines. GH alone did not affect the GHR/GHBP mRNA levels. IL-1β markedly decreased the GHR and GHBP mRNA levels (respectively, −68% and −60%, P < 0.05). Neither TNF-α nor IL-6 affected the GHR/GHBP gene expression. In conclusion, our results show that IL-1β, and TNF-α to a lesser extent, blunt the IGF-I mRNA response to GH. The resistance to GH induced by IL-1β might be mediated by a decrease of GH receptors, as suggested by the marked reduction of GHR mRNA. These findings suggest that decreased circulating IGF-I, in response to infection and trauma, may be caused by a direct effect of cytokines at the hepatocyte level.

Effect of tumor necrosis factor-α on the expression of insulin-like growth factor I and insulin-like growth factor binding protein 4 in mouse osteoblasts

1994 ◽  
Vol 131 (3) ◽  
pp. 293-301 ◽  
Author(s):  
Stephan H Scharla ◽  
Donna D Strong ◽  
Subburaman Mohan ◽  
Thierry Chevalley ◽  
Thomas A Linkhart
Keyword(s):  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Tnf Α ◽  
Igf I ◽  
Factor Α ◽  
Necrosis Factor

Scharla SH, Strong DD, Mohan S, Chevalley T, Linkhart TA. Effect of tumor necrosis factor-α on the expression of insulin-like growth factor I and insulin-like growth factor binding protein 4 in mouse osteoblasts. Eur J Endocrinol 1994;131:293–301. ISSN 0804–4643 Tumor necrosis factor-α (TNF-α) is a cytokine produced by immune cells, which has multiple effects on bone cells and is therefore thought to mediate changes in bone metabolism occurring during inflammation. In the present study we have investigated the effect of TNF-α on the secretion of insulin-like growth factor I (IGF-I) and IGF binding protein 4 (IGFBP-4) by clonal mouse osteoblasts (MC3T3-E1 cells) using subconfluent in vitro cultures and serum-free conditions. The IGF-I was determined by radioimmunoassay under conditions eliminating the interference of IGFBPs. Treatment of MC3T3-E1 cultures with TNF-α for 24 h resulted in a dose-dependent decrease in IGF-I secretion (maximally to 34 ± 9.7% of control with 60 pmol/l TNF-α; mean ± sd). The TNF-α treatment also resulted in decreased messenger ribonucleic acid (mRNA) levels of IGF-I at 4 and 24 h, as detected by Northern analysis. Because basal secretion of IGFBPs is very low in MC3T3-E1 cells, effects of TNF-α on IGFBP secretion were studied in cultures in which IGFBP-4 expression was increased by calcitriol (1,25(OH)2D3) treatment. The presence of TNF-α (600 pmol/l) inhibited this calcitriol-induced stimulation of IGFBP-4 mRNA levels from 4 h onwards, with complete inhibition of the calcitriol effect occurring at 24 h. We also observed a dose-dependent inhibition of calcitriol-stimulated IGFBP-4 secretion into the culture medium (as detected by Western ligand blot), with the maximal inhibition occurring with 600 pmol/l TFN-α to 25 ± 7% of control levels. These TNF-α effects were not prevented by indomethacin treatment, suggesting that they are not dependent on prostaglandins. The DNA synthesis was reduced to 62 ± 8% of the control value by 600 pmol/l TNF-α. We conclude that secretion of IGFs and IGFBPs by osteoblasts can be modulated by TNF-α, which in turn may be responsible for some of the known effects of TNF-α on osteoblastic cell proliferation and differentiation. Stephan H Scharla, Klinik am Kurpark, Schussenrieder Strasse 5, D-88326 Anlendorf, Germany

scholarly journals Interleukin-10 Upregulates Tumor Necrosis Factor Receptor Type-II (p75) Gene Expression in Endotoxin-Stimulated Human Monocytes

Blood ◽  
1997 ◽  
Vol 90 (10) ◽  
pp. 4162-4171 ◽  
Author(s):  
Harold L. Dickensheets ◽  
Sherry L. Freeman ◽  
Michael F. Smith ◽  
Raymond P. Donnelly
Keyword(s):  
Gene Expression ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Soluble Form ◽  
Luciferase Expression ◽  
Mrna Levels ◽  
Type Ii ◽  
Tnf Α ◽  
Ifn Γ ◽  
Necrosis Factor

Abstract Interferon-γ (IFN-γ) upregulates expression of certain genes in monocytes, including cell-surface molecules such as HLA class II, B7, and ICAM-1. IFN-γ also potentiates production of cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-12. Conversely, IL-10 downregulates expression of many of these same genes and often antagonizes the effects of IFN-γ. IL-10 is known to inhibit TNF-α production in lipopolysaccharide (LPS)-stimulated monocytes; however, the effects of IL-10 on TNF receptor (TNF-R) expression are not well defined. We examined the effects of IL-10 on production of both membrane-associated (m) and soluble (s) TNF-R type II (sTNF-RII) by purified human CD14+ monocytes. We also compared the effects of IFN-γ and IL-10 on production of TNF-α and sTNF-RII by these cells. Monocytes constitutively expressed low levels of TNF-RII mRNA and mTNF-RII protein. LPS stimulation induced rapid, but transient loss (shedding) of mTNF-RII molecules and a delayed, but marked increase in TNF-RII mRNA levels. IL-10 increased expression of both mTNF-RII and sTNF-RII by LPS-stimulated monocytes, whereas IFN-γ decreased their expression. The increased levels of sTNF-RII in cultures of IL-10–treated monocytes correlated directly with increased levels of TNF-RII mRNA and inversely with the levels of TNF-α mRNA. The ability of IL-10 to upregulate TNF-RII gene expression was transcriptionally mediated because actinomycin D blocked this effect. Furthermore, IL-10 treatment did not alter the half-life of TNF-RII mRNA transcripts in LPS-stimulated monocytes. To further examine the mechanism by which IL-10 potentiates TNF-RII gene expression, a 1.8-kb fragment of the human TNF-RII promoter cloned into a luciferase expression vector (pGL2-basic) was transfected into the IL-10–responsive macrophage cell line, RAW264.7. Although IL-10 alone induced only minimal promoter activity in these cells, it markedly increased the LPS-induced response, providing further evidence that the ability of IL-10 to amplify TNF-RII gene expression is transcriptionally controlled. Together, these findings demonstrate that IL-10 coordinately downregulates expression of TNF-α and upregulates expression of TNF-RII, particularly the soluble form of this receptor, in monocytes.

Gene expression and DNA methylation changes in BeWo cells dependent on tumor necrosis factor-α and insulin-like growth factor-I

Human Cell ◽  
2019 ◽  
Vol 33 (1) ◽  
pp. 37-46
Author(s):  
Kei Tanaka ◽  
Kazuhiko Nakabayashi ◽  
Tomoko Kawai ◽  
Shinji Tanigaki ◽  
Kenji Matsumoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Correction to: Gene expression and DNA methylation changes in BeWo cells dependent on tumor necrosis factor-α and insulin-like growth factor-I

Human Cell ◽  
2019 ◽  
Vol 33 (1) ◽  
pp. 294-294
Author(s):  
Kei Tanaka ◽  
Kazuhiko Nakabayashi ◽  
Tomoko Kawai ◽  
Shinji Tanigaki ◽  
Kenji Matsumoto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Thyroid Hormone Excess Increases Insulin-Like Growth Factor I Transcripts in Bone Marrow Cell Cultures: Divergent Effects on Vertebral and Femoral Cell Cultures*

Endocrinology ◽  
1998 ◽  
Vol 139 (5) ◽  
pp. 2527-2534 ◽  
Author(s):  
Moira Milne ◽  
Moo-Il Kang ◽  
John M. Quail ◽  
Daniel T. Baran
Keyword(s):  
Gene Expression ◽  
Bone Marrow ◽  
Alkaline Phosphatase ◽  
Growth Factor ◽  
Culture Period ◽  
Mrna Levels ◽  
Factor I ◽  
Igf I ◽  
I Gene

Abstract Thyroid hormones (T3 and T4) regulate bone development, growth, and turnover. Studies have suggested that different skeletal sites respond differently to thyroid hormones. Therefore, we examined the in vitro T3 responsiveness of cells committed to the osteoblast lineage as a function of skeletal location. Bone marrow cells derived from female rat femurs and vertebrae were cultured using conditions that induce osteogenic differentiation. Cells from both sites formed mineralized bone nodules in primary and secondary culture. In femoral cultures, collagen type I (coll I) and osteocalcin (OC) messenger RNA (mRNA) levels increased from the earliest time point examined (day 3) to a maximum on day 12 and thereafter declined to undetectable levels. T3 increased both OC and coll I mRNA, resulting in a continuous expression throughout the culture period. Insulin-like growth factor I (IGF-I) gene expression was detected at very low levels by Northern analysis of femoral total RNA, and T3 only marginally enhanced IGF-I mRNA levels. In vertebral cultures, OC and coll I mRNA levels also increased with time in culture, but remained expressed throughout the culture period. OC and coll I mRNA levels were not markedly altered in response to T3. In contrast to femoral cells, IGF-I gene expression was easily visualized in Northern blots from untreated vertebral cultures and was markedly increased by the addition of T3. The continuous presence of T3 (10−7m) in the medium for 18 days caused a marked decrease in the number of alkaline phosphatase-positive colonies formed in femoral secondary cultures, but only a slight decrease in the number in vertebral cultures. In addition, short term (6 days) exposure to T3 (10−7m) at the beginning of the culture period decreased alkaline phosphatase activity in femoral cultures, but not in vertebral cultures. These findings indicate that there are skeletal site-dependent differences in the in vitro responses of cells of the osteoblastic lineage to thyroid hormone.

Regulation of insulin-like growth factor-I (IGF-I) and IGF-binding proteins by tumor necrosis factor

1995 ◽  
Vol 269 (5) ◽  
pp. R1204-R1212 ◽  
Author(s):  
J. Fan ◽  
D. Char ◽  
G. J. Bagby ◽  
M. C. Gelato ◽  
C. H. Lang
Keyword(s):  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Binding Proteins ◽  
Tnf Alpha ◽  
Igf Binding Proteins ◽  
Factor I ◽  
Igf I ◽  
Igf Binding ◽  
Necrosis Factor

The purpose of the present study was to determine 1) whether exogenous administration of tumor necrosis factor-alpha (TNF-alpha) alters insulin-like growth factor-I (IGF-I) and IGF-binding proteins (BPs) and 2) whether the enhanced endogenous production of TNF mediates the lipopolysaccharide (LPS)-induced changes in the IGF system. The overnight infusion of murine TNF-alpha reduced circulating concentrations of both growth hormone (GH) and IGF-I in fasted rats. Furthermore, TNF-alpha decreased IGF-I content in liver, gastrocnemius muscle, and pituitary. In contrast, TNF-alpha increased IGF-I content in kidney and brain. IGFBP-1 was increased in plasma, liver, and muscle in response to TNF-alpha. In a second study, rats were injected with LPS after treatment with a neutralizing anti-TNF antibody (Ab), and blood and tissues were collected 4 h later. In LPS-treated rats, plasma concentrations of GH and IGF-I were reduced. LPS also decreased the IGF-I content in liver and skeletal muscle and increased plasma, liver, and muscle concentrations of IGFBP-1. Pretreatment with anti-TNF Ab attenuated the LPS-induced reduction in IGF-I and the increased IGFBP-1 in plasma and liver and completely prevented the decrease in IGF-I observed in muscle. In contrast, the LPS-induced decrease in plasma GH and the increased IGFBP-1 observed in muscle were unaltered by the anti-TNF Ab.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Role of arachidonic acid metabolism in transcriptional induction of tumor necrosis factor gene expression by phorbol ester.

1989 ◽  
Vol 9 (1) ◽  
pp. 252-258 ◽  
Author(s):  
J Horiguchi ◽  
D Spriggs ◽  
K Imamura ◽  
R Stone ◽  
R Luebbers ◽  
...  
Keyword(s):  
Gene Expression ◽  
Arachidonic Acid ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Leukotriene B4 ◽  
Mrna Levels ◽  
Arachidonic Acid Release ◽  
Acid Release ◽  
Tnf Gene ◽  
Necrosis Factor

The treatment of human HL-60 promyelocytic leukemia cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) is associated with induction of tumor necrosis factor (TNF) transcript. The study reported here has examined TPA-induced signaling mechanisms responsible for the regulation of TNF gene expression in these cells. Run-on assays demonstrated that TPA increases TNF mRNA levels by transcriptional activation of this gene. The induction of TNF transcripts by TPA was inhibited by the isoquinolinesulfonamide derivative H7 but not by HA1004, suggesting that this effect of TPA is mediated by activation of protein kinase C. TPA treatment also resulted in increased arachidonic acid release. Moreover, inhibitors of phospholipase A2 blocked both the increase in arachidonic acid release and the induction of TNF transcripts. These findings suggest that TPA induces TNF gene expression through the formation of arachidonic acid metabolites. Although indomethacin had no detectable effect on this induction of TNF transcripts, ketoconazole, an inhibitor of 5-lipoxygenase, blocked TPA-induced increases in TNF mRNA levels. Moreover, TNF mRNA levels were increased by the 5-lipoxygenase metabolite leukotriene B4. In contrast, the cyclooxygenase metabolite prostaglandin E2 inhibited the induction of TNF transcripts by TPA. Taken together, these results suggest that TPA induces TNF gene expression through the arachidonic acid cascade and that the level of TNF transcripts is regulated by metabolites of the pathway, leukotriene B4 and prostaglandin E2.

Regulation of insulin-like growth factor-I gene expression by growth factors in cultured vascular smooth muscle cells

1990 ◽  
Vol 125 (3) ◽  
pp. 381-386 ◽  
Author(s):  
K. E. Bornfeldt ◽  
H. J. Arnqvist ◽  
G. Norstedt
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Basic Fgf ◽  
Aortic Smooth Muscle ◽  
Factor I ◽  
Igf I ◽  
I Gene

ABSTRACT The aim of this investigation was to study the regulation of insulin-like growth factor-I (IGF-I) gene expression in cultured rat aortic smooth muscle cells. Near-confluent cells were deprived of serum for 24 h and then exposed to IGF-I, insulin, serum, basic fibroblast growth factor (basic FGF), platelet-derived growth factor (PDGF-BB; consisting of B-chain homodimer) or GH for 24 h. Levels of IGF-I mRNA were measured by solution hybridization. The level of IGF-I mRNA was markedly decreased by 10% (v/v) newborn calf serum (78 ± 4 (s.e.m.) % decrease), 1 nmol basic FGF/1 (53 ± 8%), and 1 nmol PDGF-BB/1 (40 ± 3%) when measured after 24 h. The effect of PDGF-BB was significant after 6 h and became more marked after 24 h. GH (1 nmol/l or 0.1 μmol/l or insulin (1 nmol/l had no effect after 24 h, whereas IGF-I (1 nmol/l and insulin (10 μmol/l increased IGF-I mRNA 64 ± 20% and 46±14% respectively. The increase caused by IGF-I was demonstrated after 3 h, and was most marked after 24 h. Using Northern blot analysis of cultured aortic smooth muscle cells, IGF-I transcripts of 7-4, 1.7 and 1.1–0.8 kilobases were observed. Exposure of the cells to 10% serum, 1 nmol basic FGF/1 or 1 nmol PDGF-BB/1 for 48 h increased the cell number by 104 ±7%, 64 ± 3% and 61±22% respectively, while IGF-I, insulin and GH had little effect. In conclusion, IGF-I, and high concentrations of insulin, increased IGF-I mRNA in vascular smooth muscle cells, whereas factors which were stronger mitogens decreased IGF-I gene expression. Journal of Endocrinology (1990) 125, 381–386

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