Vitamin D3 is believed to be a contributing factor to innate immunity.
Vitamin D receptor (VDR) has a positive effect on inhibiting nuclear factor κB (NF-κB)-mediated
inflammation. The underlying molecular mechanisms remain unclear, particularly in mollusks. Consequently, this study will investigate the process of
vitamin D3/VDR regulating NF-κB pathway and further explore their functions on
inflammation, autophagy, and apoptosis in abalone Haliotis discus hannai. Results showed that knockdown of VDR by using
siRNA and dsRNA of VDR in vitro and in vivo led to more intense response of NF-κB signaling to
lipopolysaccharide and higher level of apoptosis and autophagy. In addition,
1,25(OH)2D3 stimulation after VDR silencing could partially alleviate apoptosis and induce autophagy. Overexpression of VDR restricted the K48-polyubiquitin chain-dependent inhibitor of κB (IκB) ubiquitination and apoptosis-associated speck-like
protein containing CARD (ASC) oligomerization. Besides, VDR silencing resulted in increase of ASC speck formation. In further mechanistic studies, we showed that VDR can directly bind to IκB and IKK1 in vitro and in vivo. In the feeding trial, H&E staining, TUNEL, and electron microscope results showed that
vitamin D3 deficiency (0 IU/kg) could recruit more basophilic cells and increase more TUNEL-positive apoptotic cells and lipid droplets (LDs) than
vitamin D3 supplement (1000 IU/kg and 5000 IU/kg). In summary, abalone VDR plays a negative regulator role in NF-κB-mediated
inflammation via interacting with IκB and inhibiting
ubiquitin-dependent degradation of IκB.
Vitamin D3 in combination with VDR is essential to establish a delicate balance between autophagy and apoptosis in response to
inflammation.