Inhibition of lipopolysaccharide-induced inflammatory responses by an apolipoprotein AI mimetic peptide.
Previous studies suggest that high-density lipoprotein and apoAI inhibit lipopolysaccharide (LPS)-induced inflammatory responses. The goal of the current study was to test the hypothesis that the apoAI mimetic peptide L-4F exerts antiinflammatory effects similar to apoAI. Pretreatment of human umbilical vein endothelial cells (HUVECs) with LPS induced the adhesion of THP-1 monocytes. Incubation of cells with LPS and L-4F (1 to 50 microg/mL) reduced THP-1 adhesion in a concentration-dependent manner. This response was associated with a significant reduction in the synthesis of cytokines, chemokines, and adhesion molecules. L-4F reduced vascular cell adhesion molecule-1 expression induced by LPS or lipid A, whereas a control peptide (Sc-4F) showed no effect. In contrast to LPS treatment, L-4F did not inhibit IL-1beta- or tumor necrosis factor-alpha-induced vascular cell adhesion molecule-1 expression. The inhibitory effect of L-4F on LPS induction of inflammatory markers was associated with reduced binding of LPS to its plasma carrier molecule, lipopolysaccharide binding protein, and decreased binding of LPS to HUVEC monolayers. LPS and L-4F in HUVEC culture medium were fractionated by fast protein liquid chromatography and were localized to the same fractions, suggesting a physical interaction between these molecules. Proinflammatory responses to LPS are associated with the binding of lipid A to cell surface receptors. The current studies demonstrate that L-4F reduces the expression of inflammatory markers induced by LPS and lipid A and suggest that apoAI peptide mimetics may be useful in the treatment of inflammation associated with endotoxemia.
Gupta
Himanshu
H
Division of Cardiovascular Disease, Department of Medicine, University of Alabama, Birmingham, USA.
Dai
Lijun
L
Datta
Geeta
G
Garber
David W
DW
Grenett
Hernan
H
Li
Yanbing
Y
Mishra
Vinod
V
Palgunachari
Mayakonda N
MN
Handattu
Shaila
S
Gianturco
Sandra H
SH
Bradley
William A
WA
Anantharamaiah
G M
GM
White
C Roger
CR
D000209:Acute-Phase Proteins / Q000378:metabolism; D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000378:metabolism; D002448:Cell Adhesion; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000502:physiology; D008050:Lipid A / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000502:physiology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D008075:Lipoproteins, HDL / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009000:Monocytes / Q000502:physiology; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002352:Carrier Proteins; D018836:Inflammation Mediators; D008050:Lipid A; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008075:Lipoproteins, HDL; D008562:Membrane Glycoproteins; D010455:Peptides; D010713:Phosphatidylcholines; D019010:Vascular Cell Adhesion Molecule-1; D000099231:Lipopolysaccharide-Binding Protein; C472885:L-4F peptide; C472349:oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine