Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	In vitro inflammatory/anti-inflammatory effects of nitrate esters of purines
Δημιουργός/Συγγραφέας:	Maugé L. Fotopoulou T. Delemasure S. Dutartre P. [EL] Κουφάκη, Μαρία[EN] Koufaki, Maria Connat J.-L.
Εκδότης:	Elsevier
Ημερομηνία:	2014
Γλώσσα:	Αγγλικά
ISSN:	0014-2999
DOI:	10.1016/j.ejphar.2014.02.022
Άλλο:	PubMed ID: 24613657
Περίληψη:	Six purine analogues bearing a nitrate ester group (potential NO donor) were tested on human THP-1 macrophages to investigate their effects on the inflammatory response. Only three analogues increased the basal level of IL-1β. Two analogues exacerbated the inflammatory response induced by ATP but not that induced by H2O2. Only 6-[4-(6-nitroxyacetyl) piperazin-1-yl]-9H-purine (compound MK128) abolished ATP or H2O 2-induced IL-1β production in the culture medium. Similar results were reproduced on macrophages differentiated from buffy coats and stimulated with LPS. MK128 was the only analogue to release NO and leading to nitrite formation in the culture medium. The EC50 for inhibition of induced IL-1β production by the cells was estimated to be 10-12 μg/ml (about 36 μM) and corresponded to the production of around 30 μM nitrites in the culture medium. This anti-inflammatory effect of MK128 was mimicked by trinitrin used in 10 fold higher concentrations. Preincubation of cells with NO trapper cPTIO partially abolished the beneficial effect of MK128 while MK137, a ONO2 deprived analogue of MK128, was not able to inhibit induced IL-1β production and proved to be inflammatory. Moreover, purinergic channel inhibitors (oATP and U73122) inhibited the MK137 inflammatory effect. Finally, MK128 reduced the quantity of p20 caspase-1 produced in the culture medium. We suggest that MK128 inhibits IL-1β production via NO production and subsequent inflammasome component nitrosylation. On the opposite MK137, deprived from ONO2 group, could act as agonist of purinergic receptors and could thus activate inflammasome.
Τίτλος πηγής δημοσίευσης:	European Journal of Pharmacology
Τόμος/Κεφάλαιο:	730
Τεύχος:	1
Σελίδες:	148-156
Θεματική Κατηγορία:	[EL] Φαρμακευτική χημεία[EN] Pharmaceutical chemistry
Λέξεις-Κλειδιά:	ATP Caspase-1 Interleukin-1β NO donor THP-1
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2014 Published by Elsevier B.V. All rights reserved.
Σημειώσεις:	Seventh Framework Programme, FP7: 245866; Ministère de l'Enseignement Supérieur et de la Recherche, MESR; Seventh Framework Programme, FP7: FP7-REGPOT-2009-1; Conseil régional de Bourgogne-Franche-Comté. This work was supported by the French Ministère de l’Enseignement Supérieur et de la Recherche (MESR) ; Conseil Régional de Bourgogne (grants for the PARI STIC-3 project); and the European Union׳s Seventh Framework Programme (FP7-REGPOT-2009-1) under Grant agreement no. 245866 .
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο