title: The binding capability of plasma phospholipid transfer protein, but not HDL pool size, is critical to repress LPS induced inflammation.
abstract: Phospholipid transfer protein (PLTP) participates in high density lipoprotein (HDL) metabolism. Increased plasma PLTP activity was observed in lipopolysaccharide (LPS) triggered acute inflammatory diseases. This study aimed to determine the exact role of PLTP in LPS induced inflammation. HDL pool size was shrunk both in PLTP deficient mice (PLTP-/-) and PLTP transgenic mice (PLTP-Tg). PLTP displayed a strong protective effect on lethal endotoxemia in mice survival study. Furthermore, after LPS stimulation, the expression of pro-inflammatory cytokines were increased in bone marrow derived macrophage (BMDM) from PLTP-/-, while decreased in BMDM from PLTP-Tg compared with BMDM from wild-type mice (WT). Moreover, LPS induced nuclear factor kappa-B (NFκB) activation was enhanced in PLTP-/- BMDM or PLTP knockdown RAW264.7. Conversely, PLTP overexpression countered the NFκB activation in LPS challenged BMDM. Additionally, the activation of toll like receptor 4 (TLR4) induced by LPS showed no alteration in PLTP-/- BMDM. Finally, PLTP could bind to LPS, attenuate the pro-inflammatory effects of LPS, and improve the cell viability in vitro. To sum up, these findings elucidated that PLTP repressed LPS induced inflammation due to extracellular LPS binding capability, and the protective effects were not related to HDL pool size in mice.
authors: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Taian, China, 271000.|School of Basic Medicine, Taishan Medical University, Tai'an, China, 271000.
authors: Yang
authors: Y
authors: Yu
authors: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Taian, China, 271000.
authors: Yingjie
authors: Y
authors: Cui
authors: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Taian, China, 271000.
authors: Yanan
authors: Y
authors: Zhao
authors: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Taian, China, 271000.
authors: Shuai
authors: S
authors: Liu
authors: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Taian, China, 271000.|School of Basic Medicine, Taishan Medical University, Tai'an, China, 271000.
authors: Guohua
authors: G
authors: Song
authors: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Taian, China, 271000.
authors: Peng
authors: P
authors: Jiao
authors: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Taian, China, 271000.
authors: Bin
authors: B
authors: Li
authors: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Taian, China, 271000.
authors: Tian
authors: T
authors: Luo
authors: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Taian, China, 271000.
authors: Shoudong
authors: S
authors: Guo
authors: Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease and Hebei Key Laboratory of Vascular Homeostasis, Shijiazhuang, China, 050000.
authors: Xiangjian
authors: X
authors: Zhang
authors: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Taian, China, 271000.
authors: Hao
authors: H
authors: Wang
authors: Department of Anatomy and Cell Biology, SUNY Downstate Medical Center, New York, USA, 11203.
authors: Xian-Cheng
authors: XC
authors: Jiang
authors: Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis, Taishan Medical University, Taian, China, 271000.
authors: Shucun
authors: S
authors: Qin
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology* / Q000473:pathology; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D019446:Endotoxemia / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008075:Lipoproteins, HDL / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D008075:Lipoproteins, HDL; D049294:Phospholipid Transfer Proteins; C510091:phospholipid transfer protein, mouse