title: Chitosan oligosaccharides block LPS-induced O-GlcNAcylation of NF-κB and endothelial inflammatory response.
abstract: It is known that chitosan oligosaccharides (COS) suppress LPS-induced vascular endothelial inflammatory response by mechanism involving NF-κB blockade. It remains unknown how COS inhibit NF-κB. We provided evidence both in cultured endothelial cells and mouse model supporting a new mechanism. Regardless of the endothelial cell types, the LPS-induced NF-κB-dependent inflammatory gene expression was suppressed by COS, which was associated with reduced NF-κB nucleus translocation. LPS enhanced O-GlcNAc modification of NF-κB/p65 and activated NF-κB pathway, which could be prevented either by siRNA knockdown of O-GlcNAc transferase (OGT) or pretreatment with COS. Inhibition of either mitogen-activated protein kinase or superoxide generation abolishes LPS-induced NF-κB O-GlcNAcylation. Consistently, aortic tissues from LPS-treated mice presented enhanced NF-κB/p65 O-GlcNAcylation in association with upregulated gene expression of inflammatory cytokines in vascular tissues; however, pre-administration of COS prevented these responses. In conclusion, COS decreased OGT-dependent O-GlcNAcylation of NF-κB and thereby attenuated LPS-induced vascular endothelial inflammatory response.
authors.affiliation: Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; University of Chinese Academy of Sciences, Beijing 100049, China; Department of Medicine, University of Oklahoma Health Sciences Center, 941 Stanton L. Young Boulevard, Oklahoma City, OK 73104, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Hongtao
authors.initials: H
authors.lastname: Liu
authors.forename: Qing-Song
authors.initials: QS
authors.lastname: Xu
authors.forename: Yu-Guang
authors.initials: YG
authors.lastname: Du
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000215:Acylation; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D009844:Oligosaccharides / Q000737:chemistry / Q000494:pharmacology*; D021381:Protein Transport; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D009844:Oligosaccharides; D051996:Transcription Factor RelA; D048271:Chitosan; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; D000117:Acetylglucosamine
keywords: Chitosan oligosaccharides; Endothelial cells; Inflammatory response; Lipopolysaccharides (LPS); Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB); O-GlcNAcylation