Acute and prolonged effects of TNF-α on the expression and secretion of inflammation-related adipokines by human adipocytes differentiated in culture
- 488 Downloads
The pro-inflammatory cytokine TNF-α has multiple effects on adipocyte function, including the production of adipokines. In this paper, we have examined the acute vs prolonged effects of TNF-α on the expression and secretion of key inflammation-related adipokines by human adipocytes. Adipocytes differentiated in culture were treated with TNF-α for 1–24 h, mRNA quantitated by real-time polymerase chain reaction (PCR) and secreted adipokines by ELISA. Treatment of adipocytes with TNF-α for up to 24 h had little effect on MIF, MT-2 and PAI-1 mRNA levels. TNF-α decreased adiponectin, adipsin, haptoglobin and leptin mRNA levels by 24 h, but adiponectin and haptoglobin mRNA was initially increased. In contrast, TNF-α induced rapid and substantial increases in expression of the genes encoding IL-6, MCP-1, NGF and TNF-α itself; IL-6 and TNF-α 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-α, with an accelerating rate of MCP-1 secretion over 24 h. TNF-α has rapid and substantial effects on the synthesis of key inflammation-related adipokines in human adipocytes, with highly gene-specific responses.
KeywordsAdipokines Cytokines Human adipocytes Inflammation TNF-α
Monocyte chemoattractant protein-1
Macrophage migration inhibitory factor
Nerve growth factor
Plasminogen activator inhibitor-1
Tumour necrosis factor-α
Vascular endothelial growth factor
We are grateful to Mr. Leif Hunter for his help, to Dr John Jenkins for access to the ABI PRISM 7700 and to Prof. Martin Wabitsch (University of Ulm) for supplying SGBS cells. This work was funded by the European Union Framework 5 Programme (OB-AGE: OLK6-CT-2002-02288).
- 1.Bartness TJ, Bamshad M (1998) Innervation of mammalian white adipose tissue: implications for the regulation of total body fat. Am J Physiol Regul Integr Comp Physiol 44:R1399–R1411Google Scholar
- 23.Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K, Nagaretani H, Matsuda M, Komuro R, Ouchi N, Kuriyama H, Hotta K, Nakamura T, Shimomura I, Matsuzawa Y (2001) PPARγ ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 50:2094–2099PubMedCrossRefGoogle Scholar
- 32.Sakamoto T, Woodcock-Mitchell J, Marutsuka K, Mitchell JJ, Sobel BE, Fujii S (1999) TNF-α and insulin, alone and synergistically, induce plasminogen activator inhibitor-1 expression in adipocytes. Am J Physiol Cell Physiol 45:C1391–C1397Google Scholar