Dual specificity phosphatase DUSP6 promotes endothelial inflammation through inducible expression of ICAM-1

The FEBS Journal
Shu-Fang HsuTzu-Ching Meng

Abstract

Tumor necrosis factor (TNF)-α activates a diverse array of signaling pathways in vascular endothelial cells (ECs), leading to the inflammatory phenotype that contributes to the vascular dysfunction and neutrophil emigration in patients with sepsis. To date, it is not well understood what key regulator might coordinate signaling pathways to achieve inflammatory response in TNF-α-stimulated ECs. This study investigated the role of dual specificity phosphatase-6 (DUSP6) in the regulation of endothelial inflammation. Using knockout mice, we found that DUSP6 is important for TNF-α-induced endothelial intercellular adhesion molecule-1 (ICAM-1) expression in aorta and in vein. Moreover, genetic deletion of Dusp6 in pulmonary circulation significantly alleviated the susceptibility of mice to lung injury caused by neutrophil recruitment during experimental sepsis induced by TNF-α or lipopolysaccharide (LPS). The role of DUSP6 was further investigated in primary human umbilical vein endothelial cells (HUVECs). Employing RNAi approach in which endogenous DUSP6 was ablated, we showed a critical function of DUSP6 to facilitate TNF-α-induced ICAM-1 expression and endothelial leukocyte interaction. Interestingly, DUSP6-promoted endothelial in...Continue Reading

References

Jun 8, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·Q Wang, C M Doerschuk
Sep 16, 2000·Intensive Care Medicine·A C Muller KoboldJ W Tervaert
Oct 3, 2002·American Journal of Respiratory Cell and Molecular Biology·Jessica G MorelandDavid A Schwartz
Dec 20, 2002·Nature·Jonathan Cohen
Mar 29, 2003·Physiological Reviews·Alan R BurnsDavid C Walker
May 27, 2003·Nature Cell Biology·Yasuhiko KawakamiJuan Carlos Izpisúa Belmonte
Jun 20, 2003·Current Biology : CB·Maxwell C EblaghieCheryll Tickle
Jun 17, 2004·Circulation·Jean Davignon, Peter Ganz
Feb 8, 2006·American Journal of Physiology. Lung Cellular and Molecular Physiology·Abdul BasitKlaus Ley
Oct 24, 2006·Annals of the New York Academy of Sciences·Laurence J Egan, Murat Toruner
Nov 14, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Robert FürstAngelika M Vollmar
May 3, 2007·Nature Reviews. Drug Discovery·Kate L JeffreyCharles R Mackay
Aug 4, 2007·Circulation Research·Ravi M RaoFrancis W Luscinskas
Aug 25, 2007·Nature Reviews. Immunology·Klaus LeySussan Nourshargh
Dec 29, 2007·The Journal of Pathology·J R Bradley
Apr 29, 2008·European Journal of Pharmacology·Chi-Feng HungWen-Bin Wu
Sep 23, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Kieran QuinnHaibo Zhang
Oct 6, 2010·The Journal of Clinical Investigation·Zhidan WuHaiyan Xu
Nov 9, 2011·Nature Medicine·Mia Phillipson, Paul Kubes
Dec 21, 2011·Cellular Signalling·Irina Tsoy NizamutdinovaHye Jung Kim
Feb 7, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Feng QianRichard D Ye
Mar 17, 2012·Current Opinion in Infectious Diseases·Melissa A Kovach, Theodore J Standiford
Mar 6, 2013·The Journal of Pathology·John P WatersJohn R Bradley
Aug 1, 2013·Journal of the American Heart Association·David W ScottRakesh P Patel
Nov 20, 2013·Journal of Proteome Research·Karine Panico, Fabio Luis Forti

❮ Previous
Next ❯

Citations

Apr 24, 2018·The FEBS Journal·Anton M Bennett
Jun 1, 2021·Frontiers in Cardiovascular Medicine·Marlies P NozNiels P Riksen
Aug 20, 2021·Animal Cells and Systems·Banzragchgarav UnenkhuuHong Seok Kim
Oct 9, 2021·The Journal of Clinical Investigation·Kel Vin WooDavid M Ornitz
Nov 23, 2021·Frontiers in Pharmacology·Chenhui CaiTongwei Chu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.