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1 Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
2 Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands; Department of Immunology, Erasmus MC, Rotterdam, The Netherlands
3 Radiology Department, Washington University School of Medicine, St. Louis, MO, USA
4 Department of Pathology,Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands
5 Department of Immunology, Erasmus MC, Rotterdam, The Netherlands
* To whom correspondence should be addressed. E-mail: l.hofland{at}erasmusmc.nl.
Increasing evidence suggests that neuropeptides play a role in the regulatory mechanisms between the neuroendocrine and immune systems. A differential expression of the 5 known somatostatin (SS) receptors (sst1-5) has been demonstrated in human immune cells and tissues. However, little is known concerning regulation and expression of sst1-5 and the peptide SS. Therefore, we investigated the expression and the time-dependent regulation of sst1-5, SS and cortistatin (CST), a novel SS-like peptide, in human monocytes (MO), monocyte-derived macrophages (MP) and -dendritic cells (DC), in basal and lipopolysaccharide (LPS)-activated state. MO, MP and DC selectively expressed sst2 mRNA. SS mRNA was not detectable, while all samples expressed CST mRNA. Expression levels of sst2 and CST mRNA showed marked differences and were in the rank order of MP>>DC>>>MO. LPS-stimulation did not induce expression of SS or sst1,3,4,5. However, sst2 mRNA expression was significantly upregulated by stimulation with LPS. CST mRNA was upregulated as well. During differentiation of MO into MP or DC, time-dependent, significant increasing sst2 and CST mRNA levels were found. By confocal microscopy, the presence of sst2 receptors was demonstrated on MP, but not on DC. This study demonstrates for the first time a selective and inducible expression of the recently discovered CST, as well as sst2 in human monocyte-derived cells, suggesting a role for a CST-sst2 system, rather than a SS-sst2 system in these immune cell types.
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