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Stimulation of NGF expression and secretion in 3T3-L1 adipocytes by prostaglandins PGD₂, PGJ₂, and ¹²-PGJ₂

Neuroendocrine and Obesity Biology Unit, Liverpool Centre for Nutritional Genomics, School of Clinical Sciences, University of Liverpool, Liverpool, United Kingdom

Submitted 10 January 2005 ; accepted in final form 14 February 2005

Nerve growth factor (NGF) has recently been shown to be secreted from white adipocytes, its production being strongly stimulated by the proinflammatory cytokine tumor necrosis factor-. In this study, we have examined whether a series of prostaglandins and other inflammation-related factors also stimulate NGF expression and secretion by adipocytes, using 3T3-L1 cells. Although interleukin (IL)-1, IL-10, and IL-18 each induced a small decrease in NGF mRNA level in 3T3-L1 adipocytes, there was no significant effect of these cytokines on NGF secretion. A small reduction in NGF expression and/or secretion was also observed with adiponectin and prostaglandins PGE₂, PGF₂, and PGI₂. In marked contrast, prostaglandin PGD₂ induced a major, dose-dependent increase (up to 20- to 40-fold) in NGF expression and secretion. The PGD₂ metabolites, PGJ₂ and ¹²-PGJ₂, also induced major increases (up to 30-fold) in NGF production. A further metabolite of PGJ₂, 15-deoxy-^12,14-PGJ₂, a peroxisome proliferator-activated receptor- agonist, led paradoxically to a small increase in NGF mRNA level but a fall in NGF secretion. Both PGD₂ and PGJ₂ induced significant increases in NGF gene expression by 4 h after their addition. It is concluded that PGD₂ and the J series prostaglandins, PGJ₂ and ¹²-PGJ₂, can play a significant role in the regulation of NGF production by white adipocytes. These results provide support for the view that NGF is an important inflammatory response protein, as well as a target-derived neurotrophin, in white adipose tissue.

adipokines; inflammation; neurotrophin; nerve growth factor; white adipose tissue

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