15-Deoxy-Δ^12,14-prostaglandin J₂facilitates thyroglobulin production by cultured human thyrocytes

Abstract

A cyclopentenone-type prostaglandin, 15-deoxy-Delta(12, 14)-prostaglandin J(2) (15-d-PGJ(2)), has been shown to induce the cellular stress response and to be a ligand for the peroxisome proliferator-activated receptor (PPAR)-gamma. We studied its effect on the basal and thyrotropin (TSH)-induced production of thyroglobulin (TG) by human thyrocytes cultured in the presence of 10% FBS. In 15-d-PGJ(2)-treated cells in which the agent itself did not stimulate cAMP production, both the basal production of TG and the response to TSH were facilitated, including the production of TG and cAMP, whereas such production was decreased in untreated cells according to duration of culture. PGD(2) and PGJ(2), which are precursors to 15-d-PGJ(2), exhibited an effect similar to 15-d-PGJ(2). However, the antidiabetic thiazolidinediones known to be specific ligands for PPAR-gamma, and WY-14643, a specific PPAR-alpha ligand, lacked this effect. 15-d-PGJ(2) and its precursors, but not the thiazolidinediones, induced gene expression for heme oxygenase-1 (HO-1), a stress-related protein, and strongly inhibited interleukin-1 (IL-1)-induced nitric oxide (NO) production. Cyclopentenone-type PGs have been recently shown to inhibit nuclear factor-kappaB (NF-kappaB) activation via a direct and PPAR-independent inhibition of inhibitor-kappaB kinase, suggesting that, in human thyrocytes, such PGs may inhibit IL-1-induced NO production, possibly via an inhibition of NF-kappaB activation. On the other hand, sodium arsenite, a known activator of the stress response pathway, induced HO-1 mRNA expression but lacked a promoting effect on TG production. Thus 15-d-PGJ(2) and its precursors appear to facilitate TG production via a PPAR-independent mechanism and through a different pathway from the cellular stress response that is available to cyclopentenone-type PGs. Our findings reveal a novel role of these PGs associated with thyrocyte differentiation.

Effect of Prostaglandin-J2on VEGF Synthesis Depends on the Induction of Heme Oxygenase-1

“…In the present article, we demonstrated that this effect of 15d-PGJ 2 is not mediated by HO-1 activation. Similarly, Kasai et al showed that the upregulation of HO-1 was not involved in the augmentation of thyroglobulin production in 15d-PGJ 2 -treated thyrocytes (20). Thus, HO-1 is not a general mediator of 15d-PGJ 2 activities, but seems to be involved only in some of them.…”

Thyroid hormone metabolism may depend on dietary fat

“…However, other results also suggest the involvement of PUFA n-6 in the stimulation of thyroid activity. The endogenous ligand of peroxisome proliferator activated receptor γ (PPARγ) -15-deoxy-Δ 12,14 -PGJ 2 (15d PGJ 2 ) -a product of C20:4 metabolism (Forman et al, 1995) was shown to facilitate the synthesis of thyroglobulin in a functional rat epithelial cell line (Kasai et al, 2000). Taking into consideration the similar mode of regulation of thyroglobulin and TPO gene transcription (Espinoza et al, 2001), 15dPGJ 2 might represent an intermediate in the signalling pathway by which PUFA affect TPO level.…”

15-Deoxy-Δ12,14-prostaglandin J2-induced apoptosis does not require PPARγ in breast cancer cells

“…Robbins and colleagues showed that ␥-linolenic acid and 15dPGJ 2 increase the expression of catalase and other antioxidant enzymes in normal astrocytes, but not in glioma cells (68) (unpublished observations). In addition, 15dPGJ 2 induces expression of heme oxygenase-1 (22), which is cyto-protective at low levels while higher expression levels are cyto-toxic (69)(70)(71).…”