LPS induces interleukin-6 and interleukin-8 but not tumor necrosis factor-alpha in human adipocytes.
Adipose tissue-derived cytokines are presumably involved in obesity-associated pathologies including type 2 diabetes and atherosclerosis. Here we studied the lipopolysaccharide (LPS)-induced expression dynamics of tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6), IL-8 and IL-10 in human adipose tissue biopsies, in preadipocyte-derived adipocytes, and in mesenchymal stem cell (MSC)-derived adipocytes. TNFalpha, IL-6, IL-8 and IL-10 secretions by adipose tissue explants were increased 5.5-, 19.5-, 3.5- and 12.5-fold, respectively, by LPS (1 microg/mL) administration. Concordantly, IL-6 and IL-8 release was dose-dependently induced in MSC-derived adipocytes by LPS (>10 pg/mL). In contrast, TNFalpha and IL-10 remained undetectable even at the highest LPS dose (1 microg/mL) after 24h. In MSC- and preadipocyte-derived adipocytes, respectively, exposure to LPS evoked a weak and transient induction of TNFalpha mRNA whereas induction of IL-6 and IL-8 mRNA were pronounced and sustained for at least 24h. Basal glucose uptake, lipolysis and IL-6 mRNA were induced by exogenous TNFalpha (10 ng/mL) but not by IL-6 (10 ng/mL), IL-8 (100 ng/mL) and IL-10 (20 ng/mL). In this adipocyte model TNFalpha induces well known metabolic effects, but together with previous reports these data suggest that inflammation-induced TNFalpha may derive from non-adipocyte sources in adipose tissue, likely to be macrophages.
Department of Research, University Hospital, CH-4031 Basel, Switzerland; University Children's Hospital, CH-4005 Basel, Switzerland.
Matthias
M
Hoch
Alex N
AN
Eberle
Ralph
R
Peterli
Thomas
T
Peters
Dalma
D
Seboek
Ulrich
U
Keller
Beat
B
Muller
Philippe
P
Linscheid
D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D001706:Biopsy; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000494:pharmacology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000494:pharmacology; D008066:Lipolysis / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000494:pharmacology
C508606:CXCL8 protein, human; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D005947:Glucose