TY - JOUR
T1 - Constitutive and regulated expression and secretion of interferon-γ- inducible protein 10 (IP-10/CXCL10) in human adipocytes
AU - Herder, C.
AU - Hauner, H.
AU - Kempf, K.
AU - Kolb, H.
AU - Skurk, T.
N1 - Funding Information:
We thank Gabi Gornitzka, Astrid Hoffmann, Silke Ecklebe and Karin Röhrig for excellent technical assistance. This work was supported by the Federal Ministry of Health, the Federal Ministry of Education, Science, Research and Technology, the Ministry of School, Science and Research of the State of North Rhine-Westphalia and the Else Kröner-Fresenius Foundation (Bad Homburg, Germany).
PY - 2007/3
Y1 - 2007/3
N2 - 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)γ-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 IFNγ, 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 IFNγ, 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. Conclusion: 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 IFNγ, but not by LPS, which points to both similar reactivities and functional differences between adipocytes and innate immune cells.
AB - 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)γ-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 IFNγ, 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 IFNγ, 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. Conclusion: 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 IFNγ, but not by LPS, which points to both similar reactivities and functional differences between adipocytes and innate immune cells.
KW - Adipocytes
KW - CXCL10
KW - Chronic inflammation
KW - Human adipose tissue
KW - IP-10
UR - http://www.scopus.com/inward/record.url?scp=33847258328&partnerID=8YFLogxK
U2 - 10.1038/sj.ijo.0803432
DO - 10.1038/sj.ijo.0803432
M3 - Article
C2 - 16819525
AN - SCOPUS:33847258328
SN - 0307-0565
VL - 31
SP - 403
EP - 410
JO - International Journal of Obesity
JF - International Journal of Obesity
IS - 3
ER -