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Cyclooxygenase-2 [corrected] activation by endotoxin mediates the decrease in IGF1, but not in IGFBP3, [corrected]
A I Martín1, M López-Menduiña, E Castillero
1Department of Physiology, Faculty of Medicine, University Complutense of Madrid, 28040 Madrid, Spain.
Abstract:
The aim of this work was to analyse the role of cyclooxygenase-2 (Ptgs2) in endotoxin-induced decrease in Igf1 and Igf binding protein-3 (Igfbp3). For this purpose, male Wistar rats were injected with lipolysaccharide (LPS) and/or the Ptgs2 inhibitor meloxicam. LPS induced a significant decrease (P<0.01) in serum concentrations of Igf1 and Igfbp3 and their mRNAs in the liver. Meloxicam administration prevented the inhibitory effect of LPS injection on serum Igf1 and its liver mRNA. By contrast, meloxicam administration was unable to modify the inhibitory effect of LPS on Igfbp3. LPS injection also induced a decrease in GH receptor (Ghr) mRNA in the liver, and meloxicam attenuated this effect. In order to elucidate a direct action of the Ptgs2 inhibitor on the liver cells, the effect of LPS and/or meloxicam was studied in primary cultures of hepatocytes with non-parenchymal cells. LPS decreased Igf1 and Ghr but not Igfbp3 gene expression in liver cells in culture. Meloxicam administration attenuated the inhibitory effect of LPS on Igf1 mRNA, whereas it did not modify the decrease in Ghr mRNA after LPS. The effect of meloxicam on the LPS response does not seem to be mediated by changes in nitric oxide or tumour necrosis factor (Tnf) production, since meloxicam did not modify the stimulatory effect of LPS on nitric oxide or Tnfalpha gene expression both in vivo and in vitro. All these data suggest that LPS-induced Ptgs2 activation decreases Igf1 gene expression in liver cells.
Insights
Cyclooxygenase-2 (Ptgs2) activation by lipopolysaccharide (LPS) decreases insulin-like growth factor 1 (Igf1) gene expression in liver cells. A Ptgs2 inhibitor, meloxicam, prevented this LPS-induced Igf1 reduction.
Area of Science:
- Biochemistry
- Molecular Biology
- Endocrinology
Background:
- Lipopolysaccharide (LPS) is a potent endotoxin that triggers inflammatory responses.
- Insulin-like growth factor 1 (Igf1) and its binding protein 3 (Igfbp3) play crucial roles in growth and metabolism.
- Cyclooxygenase-2 (Ptgs2) is an enzyme involved in inflammation and prostaglandin synthesis.
Purpose of the Study:
- To investigate the role of Ptgs2 in LPS-induced alterations of Igf1 and Igfbp3.
- To determine the effect of a Ptgs2 inhibitor, meloxicam, on these changes.
- To explore the direct effects of LPS and meloxicam on liver cells.
Main Methods:
- Male Wistar rats were injected with LPS and/or meloxicam.
- Serum concentrations and liver mRNA levels of Igf1, Igfbp3, and Growth Hormone Receptor (Ghr) were measured.
- Primary rat hepatocyte cultures were used to study direct cellular effects.
- Nitric oxide and tumor necrosis factor-alpha (Tnf) production were assessed.
Main Results:
- LPS significantly decreased serum Igf1, Igfbp3, and their liver mRNA levels.
- Meloxicam prevented the LPS-induced decrease in Igf1 and Ghr mRNA in vivo.
- Meloxicam did not affect the LPS-induced decrease in Igfbp3.
- In vitro, LPS decreased Igf1 and Ghr gene expression in liver cells, an effect partially attenuated by meloxicam for Igf1.
- Meloxicam did not alter LPS-induced nitric oxide or Tnfalpha production.
Conclusions:
- LPS-induced Ptgs2 activation plays a role in decreasing Igf1 gene expression in liver cells.
- Ptgs2 inhibition by meloxicam can mitigate the suppressive effects of LPS on Igf1.
- The effect of LPS on Igfbp3 appears to be independent of Ptgs2 activation.
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