Sulfate glycosaminoglycan from swim bladder exerts immunomodulatory potential on macrophages via toll-like receptor 4 mediated NF-κB signaling pathways

Kun Yang; Xuejing Jia; Jing Chen; Zhuo Wang; Bingbing Song; Rui Li; Kit-Leong Cheong; Saiyi Zhong

doi:10.1016/j.ijbiomac.2024.132439

Sulfate glycosaminoglycan from swim bladder exerts immunomodulatory potential on macrophages via toll-like receptor 4 mediated NF-κB signaling pathways

Int J Biol Macromol. 2024 May 16;271(Pt 1):132439. doi: 10.1016/j.ijbiomac.2024.132439. Online ahead of print.

Authors

Kun Yang¹, Xuejing Jia¹, Jing Chen¹, Zhuo Wang¹, Bingbing Song¹, Rui Li¹, Kit-Leong Cheong¹, Saiyi Zhong²

Affiliations

¹ College of Food Science and Technology, Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Province Engineering Laboratory for Marine Biological Products, Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Provincial Science and Technology Innovation Center for Subtropical Fruit and Vegetable Processing, Zhanjiang 524088, China.
² College of Food Science and Technology, Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Province Engineering Laboratory for Marine Biological Products, Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Provincial Science and Technology Innovation Center for Subtropical Fruit and Vegetable Processing, Zhanjiang 524088, China; Shenzhen Research Institute, Guangdong Ocean University, Shenzhen 518108, China; Collaborative Innovation Center of Seafood Deep Processing, Dalian Polytechnic University, Dalian 116034, China. Electronic address: zhongsy@gdou.edu.cn.

PMID: 38761907
DOI: 10.1016/j.ijbiomac.2024.132439

Abstract

This study explored the immunomodulatory impact and potential mechanisms on macrophages RAW264.7 using a purified macromolecular sulfate glycosaminoglycan (SBSG) from the swim bladder, whose structure was similar to chondroitin sulfate A. The results showed that SBSG at 0.25-1 mg/mL increased the viability and phagocytosis of RAW264.7 cells. Meanwhile, SBSG promoted the secretion of tumor necrosis factor α (TNF-α), interleukin 10 (IL-10), and nitric oxide (NO), as well as the production of reactive oxygen species (ROS). According to the RT-PCR and Western blot data, SBSG activated TLR4-nuclear factor kappa B (NF-κB) signaling pathways, which decreased the relative mRNA and protein levels of Toll-like receptor 4 (TLR4), IκB kinase β (IKKβ), NF-κB p65, and p-NF-κB p65. The molecular docking and molecular dynamic simulation findings revealed that the main binding force between TLR4 and SBSG was conventional hydrogen bond interaction, resulting in more stable ligand receptor complexes. In summary, SBSG exhibits significant immunomodulatory potential, similar to chondroitin sulfate C. The underlying molecular mechanism involved the binding of SBSG through hydrogen bonding to TLR4 receptors, triggering the NF-κB signaling pathway to downregulate the expression of related genes and proteins. This, in turn, regulated the secretion of various cytokines that were mediated by macrophages to exert the immunity of the body.

Keywords: Immunomodulatory mechanism; Macrophages; Molecular docking; Sulfate glycosaminoglycan.