Angiotensin II-Induced Early and Late Inflammatory Responses Through NOXs and MAPK Pathways.
Angiotensin II (Ang II) dysregulation has been determined as cause or an effect of many diseases. The relationship between Ang II and reactive oxygen species (ROS), which are generated by enzymes in the nicotinamide adenine dinucleotide phosphate oxidase (NOX) family, has been the focus of many researchers for years. Inflammation in response to the activities of various NOXs with differing time-dependent characteristics was reported. It is still unclear how these factors interplay over the course of the inflammatory response and how signal transduction through mitogen-activated protein kinase (MAPK) pathways. Our study collected data on the effects of Ang II on human umbilical vascular endothelial cells (HUVECs) over a comprehensive time period. Our results demonstrated that NOXs had two time-dependent reactions in response to Ang II stimulation via MAPK pathways. First, ROS was produced only during the early inflammatory phase. NOX4 promoted more rapid generation of H2O2via the JNK pathway than generation of O2·-via ERK1/2 and p38 pathways. During both the early and late phases of the inflammatory response, NOX4 activity was transduced through the JNK pathway, whereas NOX1 and NOX2 signals were transmitted via the ERK1/2 and p38 pathways. Signal transduction via ROS generation was more likely during the early phase of the inflammatory response, and increased cytokine levels were more likely induced by the late phase of the inflammatory response.
Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Xi
http://orcid.org/0000-0003-3599-4693
X
Zhang
Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Jia
J
Yang
Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Xinyi
X
Yu
Department of Orthopaedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Si
S
Cheng
Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China. correspondzx@126.com.
Hua
H
Gan
Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People's Republic of China.
Yunfeng
Y
Xia
D000804:Angiotensin II / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D020935:MAP Kinase Signaling System / Q000276:immunology*; D019255:NADPH Oxidases / Q000276:immunology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
D016207:Cytokines; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D019255:NADPH Oxidases
MAPK; NADPH oxidases (NOXs); ROS; angiotensin II (Ang II); inflammation