Cyclooxygenase-2 [corrected] activation by endotoxin mediates the decrease in IGF1, but not in IGFBP3, [corrected] gene expression in the liver

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 (P0.01) 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.