Constitutive and regulated expression and secretion of interferon-gamma-inducible protein 10 (IP-10/CXCL10) in human adipocytes.
OBJECTIVE
Chemokine secretion by adipocytes has been postulated to initiate leukocyte infiltration in adipose tissue and might mediate an important step in the establishment of obesity-related chronic immune activation. The chemokine interferon (IFN)gamma-inducible protein-10 (IP-10/CXCL10) is a chemoattractant for various leukocyte subsets and has been implicated in the pathogenesis of atherosclerosis. This study investigates whether IP-10 is expressed in human adipocytes and whether its release is regulated by body mass index (BMI) or immunological stimuli.


METHODS
In cultures of human mature adipocytes and in vitro differentiated adipocytes, IP-10 expression under basal conditions and in the presence of IFNgamma, lipopolysaccharide (LPS) or interleukin (IL)-4 was characterized by reverse transcriptase-polymerase chain reaction, Luminex technology and immunofluorescence.


RESULTS
IP-10 was expressed and secreted constitutively in most cultures of mature adipocytes from omental and subcutaneous (s.c.) depots. The association between IP-10 release and donor BMI was not significant. In in vitro differentiated adipocytes from s.c. and mammary depots and in mature s.c. adipocytes, IP-10 secretion was strongly upregulated by IFNgamma, whereas LPS or IL-4 did not affect IP-10 expression in s.c. mature adipocytes. Immunofluorescence confirmed IP-10 expression in adipocytes with abundant lipid droplets.


CONCLUSIONS
Mature human adipocytes express and secrete the chemokine IP-10 and are thus identified as a novel cellular source of this disease-related immune mediator. IP-10 expression could be significantly induced by IFNgamma, but not by LPS, which points to both similar reactivities and functional differences between adipocytes and innate immune cells.
Herder
C
C
German Diabetes Clinic, German Diabetes Center, Leibniz Center at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany. christian.herder@ddz.uni-duesseldorf.de
Hauner
H
H
Kempf
K
K
Kolb
H
H
Skurk
T
T
D017667:Adipocytes / Q000737:chemistry* / Q000276:immunology; D000273:Adipose Tissue / Q000737:chemistry / Q000276:immunology; D000328:Adult; D015992:Body Mass Index; D001940:Breast / Q000737:chemistry / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D009852:Omentum / Q000737:chemistry
C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D008070:Lipopolysaccharides; D015847:Interleukin-4; D007371:Interferon-gamma