Mycotoxins have a potential of inducing cell senescence: A new understanding of mycotoxin immunotoxicity
Abstract
Mycotoxins result in immune dysfunction and cause immune diseases in animals and humans. However, the mechanisms of immunotoxicity involved in mycotoxins have not been fully explored, and emerging evidence suggests that these toxins may promote their immunotoxicity via cellular senescence.
Mycotoxins induce cell senescence after DNA damage, and activate signaling via the NF-& kappa;B and JNK pathways to promote the secretion of senescence-associated secretory phenotype (SASP) cytokines including IL-6, IL-8, and TNF-& alpha;. DNA damage can also over-activate or cleave poly (ADP-ribose) polymerase-1 (PARP-1), increase the expression of cell cycle inhibitory proteins p21, and p53, and induce cell cycle arrest and then senescence.
These senescent cells further down-regulate proliferation-related genes and overexpress inflammatory factors resulting in chronic inflammation and eventual immune exhaustion. Here we review the underlying mechanisms by which mycotoxins trigger cell senescence and the potential roles of SASP and PARP in these pathways.
This work will help to further understand the mechanisms of immunotoxicity involved in mycotoxins.