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The essential role of p38 MAPK in mediating the interplay of oxLDL and IL-10 in regulating endothelial cell apoptosis.
- Source :
-
European journal of cell biology [Eur J Cell Biol] 2013 Apr-May; Vol. 92 (4-5), pp. 150-9. Date of Electronic Publication: 2013 Mar 14. - Publication Year :
- 2013
-
Abstract
- Interleukin-10 (IL-10) may have therapeutic potential in various inflammatory diseases, including atherosclerosis, as it can inhibit oxLDL-induced foam cell formation and apoptosis in macrophages. This study investigated the effect of IL-10 on mitogen-activated protein kinase (MAPK) activation, and apoptosis induced by oxidized low-density lipoprotein (oxLDL) in cultured human umbilical vein endothelial cells (HUVEC). The results demonstrated that IL-10 significantly blocked the phosphorylation of p38 MAPK and c-Jun N-terminal kinase (JNK) and apoptosis induced by oxLDL. The inhibitory effect of IL-10 on oxLDL-induced apoptosis was partially dependent on reduced p38, but not JNK, phosphorylation. This study also discovered a linkage between IL-10 and p38 MAPK signaling in oxLDL-induced endothelial cell apoptosis. Interestingly, this study found that lectin-like oxidized LDL receptor-1 (LOX-1) was the only scavenger receptor, on the surface of HUVEC, that was upregulated by oxLDL and the increase in LOX-1 was not suppressed by IL-10. This study confirmed that IL-10 significantly upregulated the expression of suppressor of cytokine signaling-3 (SOCS3), whereas SOCS3 knockdown by siRNA effectively blocked the inhibitory effect of IL-10 on p38 MAPK-dependent apoptosis induced by oxLDL. These results showed for the first time, that IL-10 modulated oxLDL-induced apoptosis by upregulating SOCS3, which then interrupted p38 MAPK activation in endothelial cells. These findings support the essential role of p38 MAPK in the interplay of oxLDL and IL-10 in endothelial apoptosis.<br /> (Copyright © 2013 Elsevier GmbH. All rights reserved.)
- Subjects :
- Cells, Cultured
Enzyme Activation
Extracellular Signal-Regulated MAP Kinases metabolism
Gene Expression
Humans
JNK Mitogen-Activated Protein Kinases metabolism
Phosphorylation
Protein Processing, Post-Translational
Scavenger Receptors, Class E genetics
Scavenger Receptors, Class E metabolism
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins genetics
Suppressor of Cytokine Signaling Proteins metabolism
Up-Regulation
Apoptosis
Human Umbilical Vein Endothelial Cells physiology
Interleukin-10 physiology
Lipoproteins, LDL physiology
p38 Mitogen-Activated Protein Kinases physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1618-1298
- Volume :
- 92
- Issue :
- 4-5
- Database :
- MEDLINE
- Journal :
- European journal of cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 23498167
- Full Text :
- https://doi.org/10.1016/j.ejcb.2013.01.001