Restricted accessResearch articleFirst published online 2019-06
Forkhead Box C2 Attenuates Lipopolysaccharide-Induced Cell Adhesion via Suppression of Intercellular Adhesion Molecule-1 Expression in Human Umbilical Vein Endothelial Cells
Atherosclerosis is a chronic vascular inflammatory disease that involves diverse cell types and circulating regulatory factors, including intercellular adhesion molecule (ICAM)-1, a proinflammatory cytokine. Lipopolysaccharides (LPS) increase ICAM-1 expression and promote cell adhesion, but the mechanism is not clear. We found that LPS induced time- and dose-regulated upregulation of ICAM-1 expression and downregulation of forkhead box protein C2 (Foxc2) expression in human umbilical vein endothelial cells (HUVECs). Overexpression of Foxc2 significantly inhibited both LPS-induced ICAM-1 expression in HUVECs and LPS-induced adhesion of THP-1 cells to HUVECs. Foxc2 siRNA dramatically increased both LPS-induced ICAM-1 expression and LPS-induced adhesion of THP-1 human monocytes cells to HUVECs. We conclude that Foxc2 inhibited LPS-induced adhesion of THP-1 cells to HUVECs by suppressing ICAM-1 expression in HUVECs.
Get full access to this article
View all access options for this article.
References
1.
AnbarasanC., BavanilathaM., LatchumanadhasK., and Ajit MullasariS. (2015). ICAM-1 molecular mechanism and genome wide SNP's association studies. Indian Heart J, 67, 282–287.
2.
BaiX., WangJ., GuoY., PanJ., YangQ., ZhangM., et al. (2015). Prostaglandin E2 stimulates β1-integrin expression in hepatocellular carcinoma through the EP1 receptor/PKC/NF-κB pathway. Sci Rep, 4, 6538.
3.
CarpénO., PallaiP., StauntonD.E., and SpringerT.A. (1992). Association of intercellular adhesion molecule-1 (ICAM-1) with actin-containing cytoskeleton and alpha-actinin. J Cell Biol, 118, 1223–1234.
4.
CollinsR.G., VeljiR., GuevaraN.V., HicksM.J., ChanL., and BeaudetA.L. (2000). P-Selectin or intercellular adhesion molecule (ICAM)-1 deficiency substantially protects gainst atherosclerosis in apolipoprotein E-deficient mice. J Exp Med, 191, 189–194.
5.
GanL., LiuZ., JinW., ZhouZ., and SunC. (2015). Foxc2 enhances proliferation and inhibits apoptosis through activating Akt/mTORC1 signaling pathway in mouse preadipocytes. J Lipid Res, 56, 1471–1480.
6.
GanL., LiuZ., ChenY., DanL., FengF., LiuG., et al. (2016). Alpha-MSH and Foxc2 promote fatty acid oxidation through C/EBPbeta negative transcription in mice adipose tissue. Sci Rep, 6, 36661.
7.
GanL., LiuZ., FengF., WuT., LuoD., HuC., et al. (2018). Foxc2 coordinates inflammation and browning of white adipose by leptin-STAT3-PRDM16 signal in mice. Int J Obes (Lond), 42, 252–259.
8.
GrossM.D., BielinskiS.J., Suarez-LopezJ.R., ReinerA.P., BaileyK., ThyagarajanB., et al. (2012). Circulating soluble intercellular adhesion molecule 1 and subclinical atherosclerosis: the coronary artery risk development in young adults study. Clin Chem, 58, 411–420.
9.
GuichetP., GuelfiS., TeigellM., HoppeL., BakalaraN., BauchetL., et al. (2015). Notch1 stimulation induces a vascularization switch with pericyte-like cell differentiation of glioblastoma stem cells. Stem Cells, 33, 21–34.
10.
HayashiH., and KumeT. (2008). Foxc transcription factors directly regulate Dll4 and Hey2 expression by interacting with the VEGF-Notch signaling pathways in endothelial cells. PLoS One, 3, e2401.
11.
KimJ.K., KimH.J., ParkS.Y., CederbergA., WestergrenR., NilssonD., et al. (2005). Adipocyte-specific overexpression of FOXC2 prevents diet-induced increases in intramuscular fatty acyl CoA and insulin resistance. Diabetes, 54, 1657–1663.
12.
KumeT. (2012). The role of Foxc2 transcription factor in tumor angiogenesis. J Oncol, 2012, 204593.
13.
LabarrereC.A., DiCarloH.L., BammerlinE., HardinJ.W., KimY.M., ChaemsaithongP., et al. (2017). Failure of physiologic transformation of spiral arteries, endothelial and trophoblast cell activation, and acute atherosis in the basal plate of the placenta. Am J Obstet Gynecol, 216, 281–287.
14.
LibbyP., and AikawaM. (2002). Stabilization of atherosclerotic plaques: new mechanisms and clinical targets. Nat Med, 8, 1257–1262.
15.
LibbyP., and TherouxP. (2005). Pathophysiology of coronary artery disease. Circulation, 111, 3481–3488.
16.
LidellM.E., SeifertE.L., WestergrenR., HeglindM., GowingA., SukoninaV., et al. (2011). The adipocyte-expressed forkhead transcription factor Foxc2 regulates metabolism through altered mitochondrial function. Diabetes, 60, 427–435.
17.
LimS., BaeE., KimH.S., KimT.A., ByunK., KimB., et al. (2012). TRAF6 mediates IL-1beta/LPS-induced suppression of TGF-beta signaling through its interaction with the type III TGF-beta receptor. PLoS One, 7, e32705.
18.
LushC.W., CepinskasG., and KvietysP.R. (2000). LPS tolerance in human endothelial cells: reduced PMN adhesion, E-selectin expression, and NF-kappaB mobilization. Am J Physiol Heart Circ Physiol, 278, H853–H861.
19.
ManiS.A., YangJ., BrooksM., SchwaningerG., ZhouA., MiuraN., et al. (2007). Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. Proc Natl Acad Sci U S A, 104, 10069–10074.
20.
McDermottM.M., and Lloyd-JonesD.M. (2009). The role of biomarkers and genetics in peripheral arterial disease. J Am Coll Cardiol, 54, 1228–1237.
21.
MrukD.D., XiaoX., LydkaM., LiM.W., BilinskaB., and ChengC.Y. (2014). Intercellular adhesion molecule 1: recent findings and new concepts involved in mammalian spermatogenesis. Semin Cell Dev Biol, 29, 43–54.
22.
MuroS., CuiX., GajewskiC., MurcianoJ.C., MuzykantovV.R., and KovalM. (2003). Slow intracellular trafficking of catalase nanoparticles targeted to ICAM-1 protects endothelial cells from oxidative stress. Am J Physiol Cell Physiol, 285, C1339–C1347.
23.
NakashimaY., RainesE.W., PlumpA.S., BreslowJ.L., and RossR. (1998). Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone sites on the endothelium in the ApoE-deficient mouse. Arterioscler Thromb Vasc Biol, 18, 842–851.
24.
PietschA., ErlW., and LorenzR.L. (1996). Lovastatin reduces expression of the combined adhesion and scavenger receptor CD36 in human monocytic cells. Biochem Pharmacol, 52, 433–439.
25.
PatelS.S., ThiagarajanR., WillersonJ.T., and YehE.T. (1998). Inhibition of alpha4 integrin and ICAM-1 markedly attenuate macrophage homing to atherosclerotic plaques in ApoE-deficient mice. Circulation, 97, 75–81.
26.
ParkG., and KimJ. (2015). LPS up-regulates ICAM-1 expression in breast cancer cells by stimulating a MyD88-BLT2-ERK-linked cascade, which promotes adhesion to monocytes. Mol Cells, 38, 821–828.
27.
PradhanA.D., ShrivastavaS., CookN.R., RifaiN., CreagerM.A., and RidkerP.M. (2008). Symptomatic peripheral arterial disease in women: nontraditional biomarkers of elevated risk. Circulation, 117, 823–831.
28.
TanJ., WangY., ZhangN., and ZhuX. (2016). Induction of epithelial to mesenchymal transition (EMT) and inhibition on adipogenesis: two different sides of the same coin? Feasible roles and mechanisms of transforming growth factor beta1 (TGF-beta1) in age-related thymic involution. Cell Biol Int, 40, 842–846.
29.
ViolaJ., and SoehnleinO. (2015). Atherosclerosis—a matter of unresolved inflammation. Semin Immunol, 27, 184–193.
30.
WangT., ZhengL., WangQ., and HuY. (2018). Emerging roles and mechanisms of FOXC2 in cancer. Clin Chim Acta, 479, 84–93.
31.
ZhouX., StemmeS., and HanssonG.K. (1996). Evidence for a local immune response in atherosclerosis. CD4+ T cells infiltrate lesions of apolipoprotein-E-deficient mice. Am J Pathol, 149, 359–366.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
