PMID- 8895324
OWN - NLM
STAT- MEDLINE
DCOM- 19961217
LR  - 20131121
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 137
IP  - 11
DP  - 1996 Nov
TI  - Direct stimulatory effect of insulin-like growth factor-I on monocyte and 
      macrophage tumor necrosis factor-alpha production.
PG  - 4611-8
AB  - GH has been demonstrated to play a physiological role in the priming of 
      macrophages for tumor necrosis factor-alpha (TNF alpha) synthesis. Although 
      evidence has been presented that GH exerts this effect by an indirect mechanism, 
      the mediators of GH stimulation of TNF alpha synthesis have not been identified. 
      Because insulin-like growth factor-I (IGF-I) is a major mediator of many GH 
      effects, in the present study we investigated the direct in vitro effect of this 
      growth factor on macrophage TNF alpha production. Treatment of murine macrophages 
      with physiological concentrations of IGF-I (0.13-130 nM) enhanced both basal and 
      lipopolysaccharide-stimulated macrophage TNF alpha release and messenger RNA 
      levels. Induction of basal TNF alpha production was also observed after treatment 
      of the cells with supraphysiological concentrations of insulin (130-1300 nM). 
      Exposure of human monocytes to IGF-I led to a similar increase of basal TNF alpha 
      production and messenger RNA expression. Preexposure of macrophages with specific 
      antibodies against IGF-I and IGF-I receptor before IGF-I addition resulted in a 
      complete abrogation of the stimulatory effect of IGF-I on TNF alpha production, 
      indicating that specific binding of IGF-I to its receptor is required for 
      macrophage TNF alpha induction by IGF-I. In contrast to the stimulatory effect of 
      IGF-I, neither GH (0.1-10 micrograms/ml) nor IGF-II (0.13-130 nM) enhanced 
      macrophage TNF alpha release in vitro. To assess the role of the tyrosine kinase 
      system in mediating IGF-I-induced basal TNF alpha production, macrophages were 
      preincubated with the specific tyrosine kinase inhibitors, genistein and 
      tyrphostin A9, before IGF-I exposure. Addition of these compounds resulted in a 
      dose-dependent inhibition of the stimulatory effect of IGF-I on macrophage TNF 
      alpha release, indicating that protein tyrosine kinase activation is required for 
      TNF alpha stimulation by IGF-I. Taken together, these results demonstrate that 
      IGF-I is a monocyte/macrophage activating factor that enhances TNF alpha 
      production, and that such effect is mediated via the IGF-I receptor and involves 
      tyrosine kinase activation.
FAU - Renier, G
AU  - Renier G
AD  - Department of Nutrition, Notre-Dame Hospital Research Center, Montreal, Canada.
FAU - Clement, I
AU  - Clement I
FAU - Desfaits, A C
AU  - Desfaits AC
FAU - Lambert, A
AU  - Lambert A
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Isoflavones)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 67763-97-7 (Insulin-Like Growth Factor II)
RN  - 9002-72-6 (Growth Hormone)
RN  - DH2M523P0H (Genistein)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Inhibitors/pharmacology
MH  - Genistein
MH  - Growth Hormone/pharmacology
MH  - Humans
MH  - Insulin-Like Growth Factor I/*pharmacology
MH  - Insulin-Like Growth Factor II/pharmacology
MH  - Isoflavones/pharmacology
MH  - Kinetics
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/cytology/drug effects/*physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Monocytes/cytology/drug effects/*physiology
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors
MH  - RNA, Messenger/biosynthesis
MH  - Transcription, Genetic/drug effects
MH  - Tumor Necrosis Factor-alpha/*biosynthesis
EDAT- 1996/11/01 00:00
MHDA- 1996/11/01 00:01
CRDT- 1996/11/01 00:00
PHST- 1996/11/01 00:00 [pubmed]
PHST- 1996/11/01 00:01 [medline]
PHST- 1996/11/01 00:00 [entrez]
AID - 10.1210/endo.137.11.8895324 [doi]
PST - ppublish
SO  - Endocrinology. 1996 Nov;137(11):4611-8. doi: 10.1210/endo.137.11.8895324.