RT Journal Article
SR Electronic
T1 Anti-Inflammatory Activity of  15-Deoxy-Δ<sup>12,14</sup>-PGJ<sub>2</sub> and 2-Cyclopenten-1-one: Role  of the Heat Shock Response
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 85
OP 93
DO 10.1124/mol.64.1.85
VO 64
IS 1
A1 Angela Ianaro
A1 Armando Ialenti
A1 Pasquale Maffia
A1 Paola Di Meglio
A1 Massimo Di Rosa
A1 M. Gabriella Santoro
YR 2003
UL http://molpharm.aspetjournals.org/content/64/1/85.abstract
AB The transcription factor heat shock factor 1 (HSF1) plays a key role in the expression of several genes, such as heat shock protein (hsp) genes, which are cytoprotective against several pathological conditions, including inflammation. Cyclopentenone prostaglandins (cyPG) are able to activate HSF1 and induce the synthesis of the 70-kDa hsp (hsp70) in mammalian cells. These molecules are characterized by the presence of a reactive α,β-unsatured carbonyl group in the cyclopentane ring (cyclopentenone) which is the key structure for triggering HSF1 activation. In the present study, we investigated, in carrageenin hind-paw edema, an acute model of inflammation, the effect of double-stranded oligodeoxynucleotides with consensus HSF1 sequence as transcription factor decoys to inhibit HSF1 binding to native DNA sites. We show that HSF1 activation and hsp72 expression occurs in inflamed tissue and that this effect is associated with the remission of the inflammatory reaction. Moreover, we studied the effect of prostaglandin 15-deoxy-Δ12,14-prostaglandin (PG) J2, of its precursor, PGD2 and, for the first time in vivo, the effect of the cyclopentenone ring structure itself, 2-cyclopenten-1-one. Our results demonstrated that all agents used had anti-inflammatory properties and that this effect was associated with HSF1-induced hsp72 expression in vivo, suggesting that the use of cyclopentenone derivatives may represent a novel therapeutic approach to the treatment of inflammatory diseases.