Kaempferol Alleviates Corneal Transplantation Rejection by Inhibiting
NLRP3 Inflammasome Activation and Macrophage M1 Polarization via
Promoting Autophagy
Abstract
Corneal transplantation rejection remains a major threat to the success
rate in high-risk patients. Given the many side effects presented by
traditional immunosuppressants, there is an urgency to clarify the
mechanism of corneal transplantation rejection and to identify new
therapeutic targets. Kaempferol is a natural flavonoid that has been
proven in various studies to possess anti-inflammatory, antioxidant,
anticancer, and neuroprotective properties. However, the relationship
between kaempferol and corneal transplantation remains largely
unexplored. To address this, both in vivo and in vitro, we established a
model of corneal allograft transplantation in Wistar rats and an
LPS-induced inflammatory model in THP-1 derived human macrophages. In
the transplantation experiments, we observed an enhancement in the NLRP3
/ IL-1 β axis and in M1 macrophage polarization post-operation. In
groups to which kaempferol intraperitoneal injections were administered,
this response was effectively reduced. However, the effect of kaempferol
was reversed after the application of autophagy inhibitors. Similarly,
in the inflammatory model, we found that different concentrations of
kaempferol can reduce the LPS-induced M1 polarization and NLRP3
inflammasome activation. Moreover, we confirmed that kaempferol induced
autophagy and that autophagy inhibitors reversed the effect in
macrophages. In conclusion, we found that kaempferol can inhibit the
activation of the NLRP3 inflammasomes by inducing autophagy, thus
inhibiting macrophage polarization, and ultimately alleviating corneal
transplantation rejection. Thus, our study suggests that kaempferol
could be used as a potential therapeutic agent in the treatment of
allograft rejection.