Title:Prothymosin Alpha: An Alarmin and More...
Volume: 24
Issue: 17
Author(s): Pinelopi Samara, Chrysoula-Evangelia Karachaliou, Kyriaki Ioannou, Nikos E. Papaioannou, Ioannis F. Voutsas, Christos Zikos, Ioannis Pirmettis, Minas Papadopoulos, Hubert Kalbacher, Evangelia Livaniou, Ourania E. Tsitsilonis* Wolfgang Voelter
Affiliation:
- Section of Animal & Human Physiology, Department of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 15784,Greece
Keywords:
Prothymosin alpha, proTα(100-109), alarmin, cancer, inflammation, sepsis.
Abstract: Background/Objective: Prothymosin alpha (proTα) is a ubiquitous polypeptide first isolated
by Haritos in 1984, whose role still remains partly elusive. We know that proTα acts both, intracellularly,
as an anti-apoptotic and proliferation mediator, and extracellularly, as a biologic response
modifier mediating immune responses similarly to molecules termed as “alarmins”. Our research
team pioneered the elucidation of the mechanisms underlying the observed activities of
proTα.
Results: We were the first to demonstrate that proTα levels increase during normal and abnormal
cell proliferation. We showed that proTα acts pleiotropically, inducing immunomodulatory effects
on immune cell populations. We revealed that the immunoreactive region of proTα is the carboxyterminal
decapeptide proTα(100-109) and both molecules stimulate innate immune responses, signaling
through Toll-like receptors (TLRs), specifically TLR-4. We reported that proTα and
proTα(100-109) bind on the surface of human neutrophils on sites involving TLR-4, and cell activation
is complemented by cytoplasmic calcium ion influx. Further, we showed that proTα and
proTα(100-109) act as adjuvants upstream of lymphocyte stimulation and, in the presence of antigen,
promote the expansion of antigen-reactive effectors. Most recently, we reported that
proTα(100-109) may accumulate in experimentally inflamed sites and can serve as a surrogate biomarker
in severe bacterial infections, proposing that extracellular release of proTα or proTα(100-
109) alerts the immune system during conditions of danger.
Conclusion: We, therefore, suggest that proTα, and likely proTα(100-109), act as alarmins, being
important immune mediators as well as biomarkers, and could eventually become targets for new
therapeutic/diagnostic approaches in immune-related diseases like cancer, inflammation, and sepsis.
