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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0205v1 198/2/385    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Martin, A. I. Articles by Lopez-Calderon, A. Search for Related Content PubMed PubMed Citation Articles by Martin, A. I. Articles by Lopez-Calderon, A.

A Martin, Physiology, Complutense University, Faculty of Medicine, Madrid, Spain
M Lopez-Menduina, Physiology, Complutense University, Faculty of Medicine, Madrid, Spain
E Castillero, Physiology, Complutense University, Faculty of Medicine, Madrid, Spain
M Granado, Physiology, Complutense University, Faculty of Medicine, Madrid, Spain
M Villanua, Physiology, Complutense University, Faculty of Medicine, Madrid, Spain
A Lopez-Calderon, Physiology, Complutense University, Faculty of Medicine, Madrid, 28040, Spain

Correspondence: Asuncion Lopez-Calderon, Email: ALC{at}med.ucm.es

Abstract

The aim of this work was to analyse the role of cyclooxygenase-2 (COX-2) in endotoxin-induced decrease in insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3). For this purpose, male Wistar rats were injected with lipolysaccharide (LPS) and/or with the COX-2 inhibitor meloxicam. LPS induced a significant decrease (P<0.01) in serum concentrations of IGF-I and IGFBP-3 and in their mRNAs in the liver. Meloxicam administration prevented the inhibitory effect of LPS injection on serum IGF-I and on its liver mRNA. In contrast, meloxicam administration was unable to modify the inhibitory effect of LPS on IGFBP-3. LPS injection also induced a decrease in growth hormone (GH) receptor (GHR) mRNA in the liver, and meloxicam attenuated this effect. In order to elucidate a direct action of the COX-2 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 IGF-I and GHR but not IGFBP-3 gene expression in liver cells in culture. Meloxicam administration attenuated the inhibitory effect of LPS on IGF-I 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 TNF gene expression both in vivo and in vitro. All these data suggest that LPS-induced COX-2 activation decreases IGF-I gene expression in liver cells.