title: The lipid-bound apolipoprotein A-I cysteine mutant (N74C) inhibits the activation of NF-κB, JNK and p38 in endotoxemic mice and RAW264.7 cells.
abstract: Our previous studies showed that recombinant high-density lipoprotein (rHDL) rHDL74 exhibited higher anti-inflammatory capabilities compared to wild-type rHDL (rHDLwt), while rHDL228 showed hyper-proinflammation. In this paper, we further investigated the potential mechanisms involved in their different inflammatory functions using two models: endotoxemic mice and the RAW264.7 inflammation model. Our results showed that 24 h after the injection of lipopolysaccharide (LPS), mice treated with rHDL74 had a significant decrease in plasma CRP (P<0.01 vs. rHDLwt; P<0.01 vs. LPS), MCP-1 (P<0.05 vs. rHDLwt; P<0.01 vs. LPS) and CD14 (P<0.01 vs. LPS) compared with the mice treated with rHDLwt or the controls that received LPS only. Similar to our previous study, rHDL228 increased the plasma level of CRP (P<0.05 vs. LPS) and MCP-1 (P<0.01 vs. LPS). Our immunohistochemistry and western blot analysis showed that rHDL74 inhibited the activation of NF-κB in endotoxemic mice and JNK and p38 in the RAW264.7 inflammation model, while rHDL228 exacerbated the activation of NF-κB and ERK. In summary, our data suggest that rHDL74 exhibits higher anti-inflammatory activity by decreasing inflammatory factors and inhibiting the activation of NF-κB, JNK and p38, while rHDL228 appears to be hyper-proinflammation by increasing these inflammatory factors and aggravating the activation of NF-κB and ERK.
authors.affiliation: Gout laboratory, The Affiliated Hospital of Medical College Qingdao University, Shandong Provincial Key Laboratory Of Metabolic Diseases, Qingdao, China. wylapollo@163.com
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Wang
authors.forename: Shulai
authors.initials: S
authors.lastname: Lu
authors.forename: Xinde
authors.initials: X
authors.lastname: Li
authors.forename: Na
authors.initials: N
authors.lastname: Du
authors.forename: Yunbo
authors.initials: Y
authors.lastname: Sun
authors.forename: Jinyan
authors.initials: J
authors.lastname: Xing
authors.forename: Xinting
authors.initials: X
authors.lastname: Pan
authors.forename: Baosheng
authors.initials: B
authors.lastname: Chen
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Miao
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003545:Cysteine / Q000235:genetics*; D019446:Endotoxemia / Q000201:enzymology / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016632:Apolipoprotein A-I; D008055:Lipids; D016328:NF-kappa B; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D003545:Cysteine