PPARγ Attenuates Interleukin-1β-Induced Cell Apoptosis by Inhibiting NOX2/ROS/p38MAPK Activation in Osteoarthritis Chondrocytes
Introduction. Reactive oxygen species (ROS) induced by extracellular cytokines trigger the expression of inflammatory mediators in osteoarthritis (OA) chondrocyte. Peroxisome proliferator-activated receptor gamma (PPARγ) exerts an anti-inflammatory effect. The aim of this study was to elucidate the...
Main Authors: | , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2021-01-01
|
Series: | Oxidative Medicine and Cellular Longevity |
Online Access: | http://dx.doi.org/10.1155/2021/5551338 |
id |
doaj-f05e933dbbef453d8649b27c487b7fd6 |
---|---|
record_format |
Article |
spelling |
doaj-f05e933dbbef453d8649b27c487b7fd62021-05-17T00:00:52ZengHindawi LimitedOxidative Medicine and Cellular Longevity1942-09942021-01-01202110.1155/2021/5551338PPARγ Attenuates Interleukin-1β-Induced Cell Apoptosis by Inhibiting NOX2/ROS/p38MAPK Activation in Osteoarthritis ChondrocytesSu Ni0Dong Li1Hui Wei2Kai-Song Miao3Chao Zhuang4Laboratory of Clinical OrthopedicsDepartment of OrthopedicsDepartment of OrthopedicsDepartment of OrthopedicsDepartment of OrthopedicsIntroduction. Reactive oxygen species (ROS) induced by extracellular cytokines trigger the expression of inflammatory mediators in osteoarthritis (OA) chondrocyte. Peroxisome proliferator-activated receptor gamma (PPARγ) exerts an anti-inflammatory effect. The aim of this study was to elucidate the role of PPARγ in interleukin-1β- (IL-1β-) induced cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) expression through ROS generation in OA chondrocytes. Methods. IL-1β-induced ROS generation and chondrocyte apoptosis were determined by flow cytometry. Contents of NADPH oxidase (NOX), caspase-3, and caspase-9 were evaluated by biochemical detection. The involvement of NOX2 and mitogen-activated protein kinases (MAPKs) in IL-1β-induced COX-2 and PGE2 expression was investigated using pharmacologic inhibitors and further analyzed by western blotting. Activation of PPARγ was performed by using a pharmacologic agonist and was analyzed by western blotting. Results. IL-1β-induced COX-2 and PGE2 expression was mediated through NOX2 activation/ROS production, which could be attenuated by N-acetylcysteine (NAC; a scavenger of ROS), GW1929 (PPARγ agonist), DPI (diphenyleneiodonium chloride, NOX2 inhibitor), SB203580 (p38MAPK inhibitor), PD98059 (extracellular signal-regulated kinase, ERK inhibitor), and SP600125 (c-Jun N-terminal kinase, JNK inhibitor). ROS activated p38MAPK to enter the nucleus, which was attenuated by PPARγ. Conclusion. In OA chondrocytes, IL-1β induced COX-2 and PGE2 expression via activation of NOX2, which led to ROS production and MAPK activation. The activation of PPARγ exerted protective roles in the pathogenesis of OA.http://dx.doi.org/10.1155/2021/5551338 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Su Ni Dong Li Hui Wei Kai-Song Miao Chao Zhuang |
spellingShingle |
Su Ni Dong Li Hui Wei Kai-Song Miao Chao Zhuang PPARγ Attenuates Interleukin-1β-Induced Cell Apoptosis by Inhibiting NOX2/ROS/p38MAPK Activation in Osteoarthritis Chondrocytes Oxidative Medicine and Cellular Longevity |
author_facet |
Su Ni Dong Li Hui Wei Kai-Song Miao Chao Zhuang |
author_sort |
Su Ni |
title |
PPARγ Attenuates Interleukin-1β-Induced Cell Apoptosis by Inhibiting NOX2/ROS/p38MAPK Activation in Osteoarthritis Chondrocytes |
title_short |
PPARγ Attenuates Interleukin-1β-Induced Cell Apoptosis by Inhibiting NOX2/ROS/p38MAPK Activation in Osteoarthritis Chondrocytes |
title_full |
PPARγ Attenuates Interleukin-1β-Induced Cell Apoptosis by Inhibiting NOX2/ROS/p38MAPK Activation in Osteoarthritis Chondrocytes |
title_fullStr |
PPARγ Attenuates Interleukin-1β-Induced Cell Apoptosis by Inhibiting NOX2/ROS/p38MAPK Activation in Osteoarthritis Chondrocytes |
title_full_unstemmed |
PPARγ Attenuates Interleukin-1β-Induced Cell Apoptosis by Inhibiting NOX2/ROS/p38MAPK Activation in Osteoarthritis Chondrocytes |
title_sort |
pparγ attenuates interleukin-1β-induced cell apoptosis by inhibiting nox2/ros/p38mapk activation in osteoarthritis chondrocytes |
publisher |
Hindawi Limited |
series |
Oxidative Medicine and Cellular Longevity |
issn |
1942-0994 |
publishDate |
2021-01-01 |
description |
Introduction. Reactive oxygen species (ROS) induced by extracellular cytokines trigger the expression of inflammatory mediators in osteoarthritis (OA) chondrocyte. Peroxisome proliferator-activated receptor gamma (PPARγ) exerts an anti-inflammatory effect. The aim of this study was to elucidate the role of PPARγ in interleukin-1β- (IL-1β-) induced cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) expression through ROS generation in OA chondrocytes. Methods. IL-1β-induced ROS generation and chondrocyte apoptosis were determined by flow cytometry. Contents of NADPH oxidase (NOX), caspase-3, and caspase-9 were evaluated by biochemical detection. The involvement of NOX2 and mitogen-activated protein kinases (MAPKs) in IL-1β-induced COX-2 and PGE2 expression was investigated using pharmacologic inhibitors and further analyzed by western blotting. Activation of PPARγ was performed by using a pharmacologic agonist and was analyzed by western blotting. Results. IL-1β-induced COX-2 and PGE2 expression was mediated through NOX2 activation/ROS production, which could be attenuated by N-acetylcysteine (NAC; a scavenger of ROS), GW1929 (PPARγ agonist), DPI (diphenyleneiodonium chloride, NOX2 inhibitor), SB203580 (p38MAPK inhibitor), PD98059 (extracellular signal-regulated kinase, ERK inhibitor), and SP600125 (c-Jun N-terminal kinase, JNK inhibitor). ROS activated p38MAPK to enter the nucleus, which was attenuated by PPARγ. Conclusion. In OA chondrocytes, IL-1β induced COX-2 and PGE2 expression via activation of NOX2, which led to ROS production and MAPK activation. The activation of PPARγ exerted protective roles in the pathogenesis of OA. |
url |
http://dx.doi.org/10.1155/2021/5551338 |
work_keys_str_mv |
AT suni ppargattenuatesinterleukin1binducedcellapoptosisbyinhibitingnox2rosp38mapkactivationinosteoarthritischondrocytes AT dongli ppargattenuatesinterleukin1binducedcellapoptosisbyinhibitingnox2rosp38mapkactivationinosteoarthritischondrocytes AT huiwei ppargattenuatesinterleukin1binducedcellapoptosisbyinhibitingnox2rosp38mapkactivationinosteoarthritischondrocytes AT kaisongmiao ppargattenuatesinterleukin1binducedcellapoptosisbyinhibitingnox2rosp38mapkactivationinosteoarthritischondrocytes AT chaozhuang ppargattenuatesinterleukin1binducedcellapoptosisbyinhibitingnox2rosp38mapkactivationinosteoarthritischondrocytes |
_version_ |
1721438841336758272 |