Acute and prolonged effects of TNF-alpha on the expression and secretion of inflammation-related adipokines by human adipocytes differentiated in culture.
The pro-inflammatory cytokine TNF-alpha has multiple effects on adipocyte function, including the production of adipokines. In this paper, we have examined the acute vs prolonged effects of TNF-alpha on the expression and secretion of key inflammation-related adipokines by human adipocytes. Adipocytes differentiated in culture were treated with TNF-alpha for 1-24 h, mRNA quantitated by real-time polymerase chain reaction (PCR) and secreted adipokines by ELISA. Treatment of adipocytes with TNF-alpha for up to 24 h had little effect on MIF, MT-2 and PAI-1 mRNA levels. TNF-alpha decreased adiponectin, adipsin, haptoglobin and leptin mRNA levels by 24 h, but adiponectin and haptoglobin mRNA was initially increased. In contrast, TNF-alpha induced rapid and substantial increases in expression of the genes encoding IL-6, MCP-1, NGF and TNF-alpha itself; IL-6 and TNF-alpha mRNA levels peaked at 2 h with 75-fold and 600-fold increases, respectively. The elevated MCP-1, NGF and VEGF mRNA levels were sustained between 4 and 24 h. The adipokine secretion pattern largely paralleled cellular mRNA levels; IL-6 (transiently), MCP-1, NGF and VEGF release were stimulated by TNF-alpha, with an accelerating rate of MCP-1 secretion over 24 h. TNF-alpha has rapid and substantial effects on the synthesis of key inflammation-related adipokines in human adipocytes, with highly gene-specific responses.
Obesity Biology Unit, Liverpool Centre for Nutritional Genomics and Liverpool Obesity Research Network, School of Clinical Sciences, University of Liverpool, Liverpool L69 3GA, UK.
Bohan
B
Wang
Paul
P
Trayhurn
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000328:Adult; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008875:Middle Aged; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha