Somatostatin Is Expressed and Secreted by Human Adipose Tissue upon Infection and Inflammation
Dalma Seboek,
Philippe Linscheid,
Henryk Zulewski,
Igor Langer,
Mirjam Christ-Crain,
Ulrich Keller and
Beat Müller
Department of Research (D.S., P.L.), Division of Endocrinology, Diabetology and Clinical Nutrition (H.Z., M.C.-C., U.K., B.M.), and Department of Visceral Surgery (I.L.), University Hospitals, CH-4031 Basel, Switzerland
Address all correspondence and requests for reprints to: Dalma Seboek, Department of Research, University Hospitals, Hebelstrasse 20, CH-4031 Basel, Switzerland. E-mail: Dalma.Seboek{at}unibas.ch.
Somatostatin (SRIF) is a well-known neuroendocrine secretionproduct. SRIF expression and secretion are induced after inflammationin murine macrophages and in endotoxin-injected sheep and pigs.Because adipocytes have been demonstrated to produce numerouscytokines and peptide hormones, we investigated the expressionof SRIF and its receptors (SSTR15) in human adipose tissueafter inflammatory stimulation in vitro and in tissues frompatients with septic disease.
Preadipocyte-derived adipocytes, mesenchymal stem cell-derivedadipocytes, and mature explanted adipocytes expressed SRIF-mRNAafter endotoxin [lipopolysaccharide (LPS)] or IL-1ßtreatments. LPS- and IL-1ß-mediated SRIF-mRNA inductionwas blocked by pretreatment with dexamethasone. Using coculturesand quantitative real-time PCR, we demonstrate adipocyte SRIFinduction by secretion factors from activated peripheral bloodmononuclear cell-derived macrophages. In contrast to basal adipocytes,SRIF protein was detected in culture supernatants of LPS-treatedand of combined TNF/IL-1ß/LPS-treated adipocytes.SRIF protein was visualized by immunohistochemistry in explantedminced adipose tissue after overnight incubation in culturemedium supplemented with combined IL-1ß and LPS. Inseptic patients, expression of SRIF-mRNA and SRIF protein wasfound in visceral, but not in sc, adipose tissue. AdipocytemRNA abundance of SSTR 15 was differentially regulatedby inflammatory treatments.
Thus, human visceral adipose tissue secretes SRIF during inflammationand sepsis and expresses several SSTRs. It is tempting to speculatethat visceral adipose tissue-derived SRIF plays a modulatoryrole in the immunological and metabolic response to inflammation.
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