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.

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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