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Expression, pharmacology, and functional role of somatostatin receptor subtypes 1 and 2 in human macrophages
Author(s) -
Armani Chiara,
Catalani Elisabetta,
Balbarini Alberto,
Bagnoli Paola,
Cervia Davide
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0606417
Subject(s) - somatostatin , biology , internalization , endocrinology , medicine , receptor , somatostatin receptor , antagonist , biochemistry
Somatostatin (SRIF)‐14 is recognized as an important mediator between the nervous and the immune system, although the functional role of its receptors (sst 1 –sst 5 ) is poorly understood in humans. In our study, we demonstrate that human macrophages, differentiated from PBMC‐derived monocytes, express sst 1 and sst 2 mRNAs. sst 1 and sst 2 are mostly localized at the cell surface and display active binding sites. In particular, sst 1 /sst 2 activation results in a weak internalization of sst 1 , and the sst 2 internalization appears more efficient. At the functional level, the activation of SRIF receptors by the multiligand analogs SOM230 and KE108, but not by SRIF‐14 or cortistatin‐14, reduces macrophage viability. Their effects are mimicked by the selective activation of sst 1 and sst 2 using CH‐275 and SMS 201‐995/L‐779,976, respectively. Further, sst 1 ‐ and sst 2 ‐mediated effects are reversed by the sst 1 antagonist SRA‐880 or the sst 2 antagonist CYN 154806, respectively. CH‐275, SMS 201‐995, and L‐779,976, but not SRIF‐14, decrease mRNA expression and secretion of the MCP‐1. In addition, SRIF‐14, CH‐275, SMS 201‐995, and L‐779,976 decrease IL‐8 secretion, and they do not affect IL‐8 mRNA expression. In contrast, SRIF‐14 and sst 1 /sst 2 agonists do not affect the secretion of matrix metalloproteinase‐9. Collectively, our results suggest that the SRIF system, through sst 1 and sst 2 , 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.