Τίτλος:
Prothymosin α and Its C-Terminal Immunoreactive Decapeptide Show no Evidence of Acute Toxicity: A Preliminary in Silico, in Vitro and in Vivo Investigation.
Περίληψη:
BACKGROUND: Members of the α-thymosin family have long been studied for their immunostimulating properties. Among them, the danger-associated molecular patterns (DAMPs) prothymosin α (proTα) and its C-terminal decapeptide proTα(100-109) have been shown to act as immunomodulators in vitro, due to their ability to promote T helper type 1 (Th1) responses. Recently, we verified these findings in vivo, showing that both proTα and proTα(100-109) enhance antitumor-reactive T cell-mediated responses. METHODS: In view of the eventual use of proTα and proTα(100-109) in humans, we investigated their safety profile in silico, in human leukocytes and cancer cells lines in vitro, and in immunocompetent mice in vivo, in comparison to the proTα derivative thymosin alpha 1 (Τα1), a 28-mer peptide extensively studied for its safety in clinical trials. RESULTS: In silico prediction via computational tools showed that all three peptide sequences likely are non-toxic or do not induce allergic regions. In vitro, proTα, proTα(100-109) and Tα1 did not affect the viability of human cancer cell lines and healthy donor-derived leukocytes, did not promote apoptosis or alter cell cycle distribution. Furthermore, mice injected with proTα, proTα(100-109) and Tα1 at doses equivalent to the suggested dose regimen of Tα1 in humans, did not show signs of acute toxicity, whereas proTα and proTα(100-109) increased the levels of proinflammatory and Th1-type cytokines in their peripheral blood. CONCLUSION: Our preliminary findings suggest that proTα and proTα(100-109), even at high concentrations, are non-toxic in vitro and in an acute toxicity model in vivo; moreover, we show that the two peptides retain their immunomodulatory properties in vivo and, eventually, could be considered for therapeutic use in humans.
Συγγραφείς:
Birmpilis, Anastasios I.
Vitsos, Panagiotis
Kostopoulos, Ioannis V.
Williams, Lillian
Ioannou, Kyriaki
Samara, Pinelopi
Karachaliou, Chrysoula-Evangelia
Voutsas, Ioannis F.
Alyfanti, Elena
Angelis, Nikolaos
Gavalas, Nikolaos G.
Gkraikou, Themis
Kappa, Niki
Klagkou, Eleftheria
Klimentzou, Persefoni
Nikou, Spiridoula
Papaioannou, Nikos E.
Skopeliti, Margarita
Toukli, David
Dimopoulos, Meletios-Athanasios
Bamias, Aristotelis
Livaniou, Evangelia
Kalbacher, Hubert
Tsitsilonis, Ourania E.
Voelter, Wolfgang
Περιοδικό:
Current Medicinal Chemistry
Λέξεις-κλειδιά:
DAMP, immunomodulation, in vivo toxicity, prothymosin alpha, thymic peptides, thymosin alpha 1
DOI:
10.2174/0929867328666211117093401
