LDL uptake by monocytes in response to inflammation is MAPK dependent but independent of tribbles protein expression.
Inflammatory activation of monocytes is a hallmark event in cardiovascular disease. Activated monocytes migrate into atherosclerotic lesions, differentiate into macrophages and ingest lipids to become foam cells. These, in turn, through interaction with other inflammatory cell types contribute to plaque instability and are thought to play a key role in the development of acute coronary syndromes. In the current manuscript we investigated whether inflammatory activation of monocyte THP-1 cells influences their ability to take-up chemically modified LDL. We have also studied whether tribbles proteins, which have been shown to regulate the activation of inflammatory signal processing networks, have a modulatory role in the uptake of modified LDL by monocyte. Here, we show that activation of THP-1 cells by LPS potentiates LDL uptake. The greatest effect of LPS was seen after 16 h, compared to acute stimulation. Specific MAPK pathways are involved in this potentiation. Inhibition of both the p38 and ERK pathways led to reduced LPS uptake, specifically in LPS stimulated cells. Expression of tribbles, regulators of MAPK signalling, was dynamically modulated by LPS activation. However, neither suppression of tribbles expression by transient transfection of specific siRNAs nor transient overexpression of these proteins led to changes in the capacity of THP-1 cells to take up modified LDL. Therefore, we conclude that LPS potentiation of LDL uptake of THP-1 cells is MAPK dependent but is not mediated by tribbles.
Eder
Katalin
K
Cardiovascular Research Unit, University of Sheffield, United Kingdom.
Guan
Hongtao
H
Sung
Hye Y
HY
Francis
Sheila E
SE
Crossman
David C
DC
Kiss-Toth
Endre
E
D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D008078:Cholesterol, LDL / Q000378:metabolism*; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000037:antagonists & inhibitors; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics
D018797:Cell Cycle Proteins; D008078:Cholesterol, LDL; D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D012097:Repressor Proteins; C493170:TRIB1 protein, human; C474831:TRIB3 protein, human; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C489044:TRIB2 protein, human; D020928:Mitogen-Activated Protein Kinases