Adiponectin inhibits tumor necrosis factor-α-induced vascular inflammatory response via caveolin-mediated ceramidase recruitment and activation.

Authors

Yajing Wang, Department of Emergency Medicine, Thomas Jefferson UniversityFollow
Xiaoliang Wang, Department of Emergency Medicine, Thomas Jefferson UniversityFollow
Wayne Bond Lau, Department of Emergency Medicine, Thomas Jefferson UniversityFollow
Yuexing Yuan, Department of Emergency Medicine, Thomas Jefferson UniversityFollow
David Booth, Department of Pathology, Thomas Jefferson University
Jing-Jing Li, Department of Emergency Medicine, Thomas Jefferson University
Rosario Scalia, Department of Physiology, Cardiovascular Research Center, Temple UniversityFollow
Kyle Preston, Department of Physiology, Cardiovascular Research Center, Temple University
Erhe Gao, Center for Translational Medicine, Temple UniversityFollow
Walter Koch, Center for Translational Medicine, Temple UniversityFollow
Xin-Liang Ma, Department of Emergency Medicine, Thomas Jefferson University; Department of Medicine, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

2-28-2014

Comments

This article has been peer reviewed. It was published in: Circulation Research.

Volume 114, Issue 5, 28 February 2014, Pages 792-805.

The published version is available at DOI: 10.1161/CIRCRESAHA.114.302439

Copyright © 2014 American Heart Association, Inc.

Abstract

RATIONALE: Anti-inflammatory and vascular protective actions of adiponectin are well recognized. However, many fundamental questions remain unanswered.

OBJECTIVE: The current study attempted to identify the adiponectin receptor subtype responsible for adiponectin's vascular protective action and investigate the role of ceramidase activation in adiponectin anti-inflammatory signaling.

METHODS AND RESULTS: Adiponectin significantly reduced tumor necrosis factor (TNF)α-induced intercellular adhesion molecule-1 expression and attenuated TNFα-induced oxidative/nitrative stress in human umbilical vein endothelial cells. These anti-inflammatory actions were virtually abolished by adiponectin receptor 1 (AdipoR1-), but not AdipoR2-, knockdown (KD). Treatment with adiponectin significantly increased neutral ceramidase (nCDase) activity (3.7-fold; P87% of adiponectin-induced nCDase activation was lost. Whereas adiponectin treatment failed to inhibit TNFα-induced intercellular adhesion molecule-1 expression, treatment with sphingosine-1-phosphate or SEW (sphingosine-1-phosphate receptor agonist) remained effective in Cav1-KD cells. AdipoR1 and Cav1 colocalized and coprecipitated in human umbilical vein endothelial cells. Adiponectin treatment did not affect this interaction. There is weak basal Cav1/nCDase interaction, which significantly increased after adiponectin treatment. Knockout of AdipoR1 or Cav1 abolished the inhibitory effect of adiponectin on leukocyte rolling and adhesion in vivo.

CONCLUSIONS: These results demonstrate for the first time that adiponectin inhibits TNFα-induced inflammatory response via Cav1-mediated ceramidase recruitment and activation in an AdipoR1-dependent fashion.

Recommended Citation

Wang, Yajing; Wang, Xiaoliang; Lau, Wayne Bond; Yuan, Yuexing; Booth, David; Li, Jing-Jing; Scalia, Rosario; Preston, Kyle; Gao, Erhe; Koch, Walter; and Ma, Xin-Liang, "Adiponectin inhibits tumor necrosis factor-α-induced vascular inflammatory response via caveolin-mediated ceramidase recruitment and activation." (2014). Department of Medicine Faculty Papers. Paper 117.
https://jdc.jefferson.edu/medfp/117

PubMed ID

24397980