Thymopentin down-regulates both activity and expression of iNOS in blood cells of Sézary syndrome patients.
While thymopentin has been used for many years in the experimental treatment of Sézary syndrome (SS), a rare and very aggressive lymphoma, its mechanism of action is still not known. Herein we show that this peptide acts as an inhibitor of isolated iNOS and nNOS isoforms, and reduces iNOS protein/mRNA levels and iNOS activity in blood cells obtained from both healthy donors and SS patients. Similar results were obtained with TPN-2, the N(ω)-nitro analogue of the Arg-Lys motif present in thymopentin. Additional investigations are necessary to confirm the role and the relative importance of the two mechanisms of iNOS down-regulation in the therapeutic action of these peptides against SS.
Department of Medicine and Aging Science, University G. d'Annunzio of Chieti-Pescara, Via dei Vestini 31, 66013 Chieti, Italy. antoniapatruno@unich.it
Antonia
A
Patruno
Paolo
P
Tosco
Emily
E
Borretto
Sara
S
Franceschelli
Paolo
P
Amerio
Mirko
M
Pesce
Stefano
S
Guglielmo
Pietro
P
Campiglia
Maria Grazia
MG
Bernengo
Roberta
R
Fruttero
D000704:Analysis of Variance; D000818:Animals; D016022:Case-Control Studies; D002417:Cattle; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D008958:Models, Molecular; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000097:blood* / Q000235:genetics; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D012751:Sezary Syndrome / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology*; D016305:Thymopentin / Q000494:pharmacology*
D011994:Recombinant Proteins; C496319:NOS2 protein, human; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D016305:Thymopentin