Stimulation of NGF expression and secretion in 3T3-L1 adipocytes by prostaglandins PGD₂, PGJ₂, and Δ¹²-PGJ₂

Abstract

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-α. 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)-1β, 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 PGE 2 , PGF 2α , and PGI 2 . In marked contrast, prostaglandin PGD 2 induced a major, dose-dependent increase (up to 20- to 40-fold) in NGF expression and secretion. The PGD 2 metabolites, PGJ 2 and Δ 12 -PGJ 2 , also induced major increases (up to 30-fold) in NGF production. A further metabolite of PGJ 2 , 15-deoxy-Δ 12,14 -PGJ 2 , a peroxisome proliferator-activated receptor-γ agonist, led paradoxically to a small increase in NGF mRNA level but a fall in NGF secretion. Both PGD 2 and PGJ 2 induced significant increases in NGF gene expression by 4 h after their addition. It is concluded that PGD 2 and the J series prostaglandins, PGJ 2 and Δ 12 -PGJ 2 , 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.