Octreotide regulates CC but not CXC LPS-induced chemokine secretion in rat Kupffer cells
Article first published online: 30 JAN 2009
2004 British Pharmacological Society
British Journal of Pharmacology
Volume 141, Issue 3, pages 477–487, February 2004
How to Cite
Valatas, V., Kolios, G., Manousou, P., Notas, G., Xidakis, C., Diamantis, I. and Kouroumalis, E. (2004), Octreotide regulates CC but not CXC LPS-induced chemokine secretion in rat Kupffer cells. British Journal of Pharmacology, 141: 477–487. doi: 10.1038/sj.bjp.0705633
- Issue published online: 30 JAN 2009
- Article first published online: 30 JAN 2009
- (Received November 3, 2003, Accepted November 13, 2003)
- Kupffer cell(s);
- sinusoidal cell(s);
Kupffer cells (KC) and lipopolysaccharide (LPS) interaction is the initial event leading to hepatic inflammation and fibrosis in many types of liver injury. We studied chemokine secretion by KC activated with LPS and the possible effect of the somatostatin analogue octreotide, in the regulation of this process.
KC isolated from Sprague–Dawley rats were cultured in the presence of LPS added alone or with different concentrations of octreotide for 24 and 48 h, and chemokine production was assessed in culture supernatants by ELISA. CC chemokine mRNA expression was assessed by semiquantitative RT–PCR.
Vehicle-stimulated KC produced a basal amount of CC and CXC chemokines. LPS-stimulated KC secreted significantly increased amounts of IL-8 (GRO/CINC-1) (P<0.001), MIP-2 (P<0.001), MCP-1 (P<0.001), and RANTES (P<0.01).
Octreotide inhibited LPS-induced secretion of the CC chemokines MCP-1 (P<0.05) and RANTES (P<0.05), but not the CXC chemokines IL-8 (GRO/CINC-1) and MIP-2, in a concentration-dependent manner. Downregulation of basal and LPS-induced mRNA expression of the CC chemokines was also observed in the presence of octreotide.
Pretreatment with phosphatidylinositol 3 (PI3)-kinase inhibitors reduced chemokine production by LPS-treated KC in both the mRNA and protein level. Furthermore, it prevented the octreotide inhibitory effect on LPS-induced chemokine secretion, indicating a possible involvement of the PI3-kinase pathway.
In conclusion, these data demonstrate that chemokine secretion by KC can be differentially regulated by octreotide, and suggest that this somatostatin analogue may have immunoregulatory effects on resident liver macrophages.
British Journal of Pharmacology (2004) 141, 477–487. doi:10.1038/sj.bjp.0705633