Title:Prothymosin α and its C-Terminal Immunoreactive Decapeptide
Show No Evidence of Acute Toxicity: A Preliminary In Silico, In Vitro
and In Vivo Investigation
Volume: 29
Issue: 42
关键词:
潮湿，前胸腺素α，体内毒性，免疫调节，胸腺肽，胸腺素α1。
摘要:
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 cell 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, pro-
Tα, 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.
