Expression of somatostatin, cortistatin, and somatostatin receptors in human monocytes, macrophages, and dendritic cells.
Increasing evidence suggests that neuropeptides play a role in the regulatory mechanisms between the neuroendocrine and immune systems. A differential expression of the five 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 the basal and lipopolysaccharide (LPS)-activated state. MO, MP, and DC selectively expressed sst2 mRNA. SS mRNA was not detectable, whereas 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 upregulated significantly by stimulation with LPS. CST mRNA was upregulated as well. During differentiation of MO in MP or DC, time-dependent, significantly 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.
Dalm
Virgil A S H
VA
Dept. of Internal Medicine, Rm. Bd 240, Erasmus MC, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands. l.hofland@erasmusmc.nl
van Hagen
P Martin
PM
van Koetsveld
Peter M
PM
Achilefu
Sam
S
Houtsmuller
Adriaan B
AB
Pols
David H J
DH
van der Lely
Aart-Jan
AJ
Lamberts
Steven W J
SW
Hofland
Leo J
LJ
D003713:Dendritic Cells / Q000737:chemistry*; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D015870:Gene Expression; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000737:chemistry*; D018613:Microscopy, Confocal; D009000:Monocytes / Q000737:chemistry*; D009479:Neuropeptides / Q000235:genetics*; D015282:Octreotide; D012333:RNA, Messenger / Q000032:analysis; D017481:Receptors, Somatostatin / Q000032:analysis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000235:genetics*
D008070:Lipopolysaccharides; D009479:Neuropeptides; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; C099323:cortistatin; D013004:Somatostatin; C093733:somatostatin receptor 2; D016650:Fluorescein-5-isothiocyanate; D015282:Octreotide