Vitamin D3 deficiency induced intestinal inflammatory response of turbot through nuclear factor-κB/inflammasome pathway, accompanied by the mutually exclusive apoptosis and autophagy

• Published in: Frontiers in Immunology
• Main Authors: Chen, Zhichu, Huang, Dong, Yongyut, Prakaiwan, Li, Guangbin, Esteban, María Ángeles, Jintasataporn, Orapint, Deng, Junming, Zhang, Wenbing, Ai, Qinghui, Mai, Kangsen, Zhang, Yanjiao
• Other Authors: National Natural Science Foundation of China, Agriculture Research System of China, National Key Research and Development Program of China
• Format: Article in Journal/Newspaper
• Language: unknown
• Published: Frontiers Media SA 2022
• Subjects: Immunology; Immunology and Allergy; Turbot
• Online Access: http://dx.doi.org/10.3389/fimmu.2022.986593; https://www.frontiersin.org/articles/10.3389/fimmu.2022.986593/full

Vitamin D 3 (VD 3 ) participated widely in the nuclear factor-κB (NF-κB)-mediated inflammation, apoptosis, and autophagy through the vitamin D receptor (VDR). However, the molecular mechanisms remain not understood in teleost. The present study investigated the functions of VD 3 /VDR on intestinal inflammation, autophagy, and apoptosis of turbot in vivo and in vitro . Triple replicates of 30 fish were fed with each of three diets with graded levels of 32.0 (D 0 ), 1012.6 (D 1 ), and 3978.2 (D 2 ) IU/kg VD 3 . Obvious intestinal enteritis was observed in the D 0 group and followed with dysfunction of intestinal mucosal barriers. The intestinal inflammatory response induced by VD 3 deficiency was regulated by the NF-κB/inflammasome signalling. The promotion of intestinal apoptosis and suppression of intestinal autophagy were also observed in the D 0 group. Similarly, VD 3 deficiency in vitro induced more intense inflammation regulated by NF-κB/inflammasome signalling. The mutually exclusive apoptosis and autophagy were also observed in the group without 1,25(OH) 2 D 3 in vitro , accompanied by similar changes in apoptosis and autophagy increased apoptosis. The gene expression of VDRs was significantly increased with the increasing VD 3 supplementation both in vivo and in vitro . Moreover, VDR knockdown in turbot resulted in intestinal inflammation, and this process relied on the activation of inflammasome mediated by NF-κB signalling. Simultaneously, intestinal apoptosis was promoted, whereas intestinal autophagy was inhibited. In conclusion, VD 3 deficiency could induce intestinal inflammation via activation of the NF-κB/inflammasome pathway, intestinal apoptosis, and autophagy formed a mutually exclusive relation in teleost. And VDR is the critical molecule in those processes.