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Cortistatin Rather Than Somatostatin as a Potential Endogenous Ligand for Somatostatin Receptors in the Human Immune System

Departments of Internal Medicine (V.A.D., P.M.v.H., P.M.v.K., A.-J.v.d.L., S.W.L., L.J.H.) and Immunology (P.M.v.H., A.W.L.), Erasmus Medical Center, 3015 GD, Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: L. J. Hofland, Ph.D., Department of Internal Medicine, Room BD277, Erasmus Medical Center, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands. E-mail: hofland{at}inw3.fgg.eur.nl.

Cells of the human immune system have been shown to express somatostatin receptors (sst). The expression of sst suggests a functional role of the peptide somatostatin (SS). However, SS expression has not been demonstrated yet in different human immune tissues. Therefore, we investigated by RT-PCR the expression of both SS and cortistatin (CST), a SS-like peptide, in various human lymphoid tissues and immune cells. We detected SS mRNA expression in the human thymus only, while not in thymocytes. CST mRNA was clearly expressed in the immune cells, lymphoid tissues, and bone marrow. Using quantitative RT-PCR, significant differences in expression levels between tissues were demonstrated. Expression of CST mRNA was up-regulated during differentiation of monocytes into macrophages and dendritic cells and could be up-regulated by lipopolysaccharide stimulation. Two differently sized cDNA fragments of CST were detected in the majority of cells and tissues. However, although both fragments were detected in nearly all T-cell lines (7 of 8), most of the B-cell lines expressed the short fragment only (8 of 10). Using autoradiography, we showed that CST displaced [¹²⁵I-Tyr³]octreotide binding with relatively high affinity on human thymic tissue and sst₂-expressing cells. This is the first extensive study demonstrating that human lymphoid tissues and immune cells express different levels of CST mRNA and that its expression can be regulated. On the basis of these observations, we hypothesize a role for CST as an endogenous ligand of at least the sst₂ receptor in the human immune system, rather than SS itself.

This work was supported by a grant from the Dutch Organization for Scientific Research (NWO).

Abbreviations: CST, Cortistatin; HPRT, hypoxanthine-guanine phosphoribosyl transferase; LPS, lipopolysaccharide; PBMC, peripheral blood mononuclear cells; Q-PCR, quantitative RT-PCR; SS, somatostatin; sst, somatostatin receptor(s); TEC, thymic epithelial cells.

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