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|Title:||Expression, pharmacology and functional role of somatostatin receptor subtypes 1 and 2 in human macrophages||Authors:||Armani, Chiara
|Keywords:||Neuropeptides;Monocytes;Trafficking;Cell viability;Chemokines;Metalloproteinases||Issue Date:||2007||Publisher:||Society for Leukocyte Biology||Source:||Armani, C. et al. 2007. Expression, pharmacology and functional role of somatostatin receptor subtypes 1 and 2 in human macrophages. "Journal of Leukocyte Biology" 81(3): 845-855||Abstract:||
Somatostatin (SRIF)-14 is recognized as an important mediator between the nervous and the immune system, although the functional role of its receptors (sst1-sst5) is poorly understood in humans. In our study, we demonstrate that human macrophages differentiated from peripheral blood mononuclear cell-derived monocytes express both sst1 and sst2 mRNAs. Both sst1 and sst2 are mostly localized at the cell surface and display active binding sites. In particular, sst1/sst2 activation results in a weak internalization of sst1 while the sst2 internalization appears more efficient. At the functional level, the activation of SRIF receptors by the multiligand analogues SOM230 and KE108, but not by SRIF-14 or cortistatin-14, reduces macrophage viability. Their effects are mimicked by the selective activation of sst1 and sst2 using CH-275 and SMS 201-995/L-779,976, respectively. Further, both sst1- and sst2-mediated effects are reversed by the sst1 antagonist SRA-880 or the sst2 antagonist CYN, respectively. CH-275, SMS 201-995 and L-779,976, but not SRIF-14, decrease both mRNA expression and secretion of the monocyte chemotactic protein-1. In addition, SRIF-14, CH-275, SMS 201-995 and L-779,976 decrease interleukine-8 secretion while they do not affect interleukine-8 mRNA expression. In contrast, SRIF-14 and sst1/sst2 agonists do not affect the secretion of matrix metalloproteinase-9. Collectively, our results suggest that the SRIF system, through sst1 and sst2, exerts mainly an immunosuppressive effect in human macrophages and may, therefore, represent a therapeutic window that can be exploited for the development of new strategies in pharmacological therapy of inflammation.
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