title: C-type natriuretic peptide attenuates LPS-induced endothelial activation: involvement of p38, Akt, and NF-κB pathways.
abstract: Endothelial activation elicited by inflammatory agents is regarded as a key event in the pathogenesis of several vascular inflammatory diseases. In the present study, the inhibitory effects and underlying mechanism of C-type natriuretic peptide (CNP) on LPS-induced endothelial activation were examined in human umbilical vein endothelial cells (HUVECs). The effect of CNP on adhesion molecule expression was assessed using quantitative real-time RT-PCR and western blotting analyses. The nuclear factor-κB (NF-κB), MAPK, and PI3K/Akt signaling pathways in LPS-stimulated HUVECs were investigated using western blotting analyses, and the production of intracellular reactive oxygen species (ROS) was measured using a fluorescence method. Pretreatment with CNP inhibited LPS-induced expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and P-selectin in a concentration-dependent manner. CNP suppressed the phosphorylation of p65 and NF-κB activation in LPS-stimulated cells. Moreover, CNP reduced ERK1/2 and p38 phosphorylation induced by LPS but not JNK. Furthermore, CNP induced Akt phosphorylation and activation of hemeoxygenase-1 (HO-1) expression. CNP significantly inhibited the production of intracellular ROS. These results suggest that CNP effectively attenuated LPS-induced endothelial activation by inhibiting the NF-κB and p38 signaling pathways, eliminating LPS-induced intracellular ROS production, and activating the PI3K/Akt/HO-1 pathway in HUVECs; thereby, demonstrating that CNP may be a potential therapeutic target for the treatment of sepsis and inflammatory vascular diseases.
authors.affiliation: Institute of Transfusion Medicine, Academy of Military Medical Sciences, No. 27th Taiping Road, Haidian, Beijing, China.
authors.forename: Gan
authors.initials: G
authors.lastname: Chen
authors.forename: Jingxiang
authors.initials: J
authors.lastname: Zhao
authors.forename: Yujing
authors.initials: Y
authors.lastname: Yin
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Liu
authors.forename: Penglong
authors.initials: P
authors.lastname: Li
authors.forename: Lian
authors.initials: L
authors.lastname: Zhao
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
mesh_terms: D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D020098:Natriuretic Peptide, C-Type; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases