Tumor necrosis factor alpha stimulates cathepsin K and V activity via juxtacrine monocyte-endothelial cell signaling and JNK activation.

Molecular and Cellular Biochemistry
Philip M KeeganManu O Platt

Abstract

Inflammation and damage promote monocyte adhesion to endothelium and cardiovascular disease (CVD). Elevated inflammation and increased monocyte-endothelial cell interactions represent the initial stages of vascular remodeling associated with a multitude of CVDs. Cathepsins are proteases produced by both cell types that degrade elastin and collagen in arterial walls, and are upregulated in CVD. We hypothesized that the inflammatory cytokine tumor necrosis factor alpha (TNFα) and monocyte binding would stimulate cathepsins K and V expression and activity in endothelial cells that may be responsible for initiating local proteolysis during CVD. Confluent human aortic endothelial cells were stimulated with TNFα or THP-1 monocyte co-cultures, and multiplex cathepsin zymography was used to detect changes in levels of active cathepsins K, L, S, and V. Direct monocyte-endothelial cell co-cultures stimulated with TNFα generated maximally observed cathepsin K and V activities compared to either cell type alone (n = 3, p < 0.05) by a c-Jun N-terminal kinase (JNK)-dependent manner. Inhibition of JNK with SP6000125 blocked upregulation of cathepsin K activity by 49 % and cathepsin V by 81 % in endothelial cells. Together, these data show tha...Continue Reading

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Citations

Jul 12, 2013·Critical Care : the Official Journal of the Critical Care Forum·Khodor IssaBruno Levy
Oct 16, 2015·Biochimie·Manu O Platt, W Andrew Shockey
Dec 22, 2016·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Akia N ParksJohnna S Temenoff
Oct 21, 2015·Reproductive Sciences·Kristi M PorterManu O Platt
Jan 15, 2017·Acta Biomaterialia·Brenton JennewineAnand Ramamurthi
Nov 10, 2018·Tissue Engineering. Part a·Lauren GrantRashid Bashir
Nov 2, 2012·Integrative Biology : Quantitative Biosciences From Nano to Macro·Keon-Young ParkManu O Platt
Mar 13, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Hannah SongManu O Platt
Jun 1, 2018·Oxidative Medicine and Cellular Longevity·Jingyuan SunLing Gao
Apr 26, 2020·International Journal of Molecular Sciences·Chia-Liang LinChien-Min Chen
Jan 12, 2020·Biochimica Et Biophysica Acta. Proteins and Proteomics·Xian ZhangGuo-Ping Shi
Mar 7, 2021·International Journal of Molecular Sciences·Rita MorettiClaudio Tiribelli
Apr 1, 2021·Protein Science : a Publication of the Protein Society·Keval BollavaramManu O Platt

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