IL-6 trans-Signaling Impairs Sprouting Angiogenesis by Inhibiting Migration, Proliferation and Tube Formation of Human Endothelial Cells.

Cells
Mulugeta M ZegeyeLiza U Ljungberg

Abstract

Sprouting angiogenesis is the formation of new capillaries from existing vessels in response to tissue hypoxia due to growth/development, repair/healing, and also chronic inflammation. In this study, we aimed to elucidate the effect of IL-6, a pleiotropic cytokine with both pro-inflammatory and anti-inflammatory functions, in regulating the sprouting angiogenic response of endothelial cells (ECs). We found that activation of IL-6 trans-signaling inhibited the migration, proliferation, and tube formation ability of ECs. In addition, inhibition of the autocrine IL-6 classic-signaling by depleting endogenous IL-6 from ECs impaired their tube formation ability. At the molecular level, we found that IL-6 trans-signaling in ECs upregulated established endogenous anti-angiogenic factors such as CXCL10 and SERPINF1 while at the same time downregulated known endogenous pro-angiogenic factors such as cKIT and CXCL8. Furthermore, prior activation of ECs by IL-6 trans-signaling alters their response to vascular endothelial growth factor-A (VEGF-A), causing an increased p38, but decreased Erk1/2 phosphorylation. Collectively, our data demonstrated the dual facets of IL-6 in regulating the sprouting angiogenic function of ECs. In addition, w...Continue Reading

References

Mar 11, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Rebecca StarkieBente Klarlund Pedersen
Jun 5, 2003·Nature Medicine·Napoleone FerraraJennifer LeCouter
Jul 15, 2003·American Journal of Physiology. Endocrinology and Metabolism·Adam SteensbergBente Klarlund Pedersen
Feb 22, 2005·Current Drug Targets. Inflammation and Allergy·Antonella Naldini, Fabio Carraro
Aug 22, 2006·Current Pharmaceutical Design·R BenelliD M Noonan
Nov 1, 2006·Nature Clinical Practice. Rheumatology·Norihiro Nishimoto, Tadamitsu Kishimoto
Mar 31, 2007·Circulation Research·Laurent LamaliceJacques Huot
Apr 26, 2007·Angiogenesis·Carla CostaRaquel Soares
May 25, 2007·Nature Reviews. Molecular Cell Biology·Ralf H Adams, Kari Alitalo
Mar 14, 2008·Blood·Richard C A SainsonChristopher C W Hughes
May 16, 2009·Arteriosclerosis, Thrombosis, and Vascular Biology·Qi XueLaura E Benjamin
Mar 13, 2010·Nature Protocols·Irina Arnaoutova, Hynda K Kleinman
Feb 8, 2011·Biochimica Et Biophysica Acta·Jürgen SchellerStefan Rose-John
Sep 20, 2011·Cell·Michael PotentePeter Carmeliet
Feb 14, 2012·The EMBO Journal·Guo-Xiang Ruan, Andrius Kazlauskas
Jul 5, 2012·Cold Spring Harbor Perspectives in Medicine·Sina Koch, Lena Claesson-Welsh
Jul 21, 2012·PloS One·Cecelia C Yates-BinderTimothy Turner
Dec 18, 2013·Bioinformatics·Andreas KrämerStuart Tugendreich
Jul 21, 2015·Cytokine & Growth Factor Reviews·Fred Schaper, Stefan Rose-John
Feb 20, 2016·Oncology Letters·Jun Shi, Pin-Kang Wei
Nov 12, 2016·Journal of the American Society of Nephrology : JASN·Rusan CatarAchim Jörres
Feb 18, 2017·Redox Biology·Caroline CamaréRobert Salvayre
Aug 15, 2017·BioMed Research International·Francesco Paolo CantatoreDomenico Ribatti
May 14, 2019·Oncotarget·Mai Tanaka, Dietmar W Siemann
Jul 12, 2019·Frontiers in Immunology·Erin Fahey, Sarah L Doyle
Aug 23, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Koung Li KimWonhee Suh
Jan 11, 2020·Frontiers in Oncology·Dolores Aguilar-CazaresJose S Lopez-Gonzalez

❮ Previous
Next ❯

Citations

Mar 5, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Mulugeta M ZegeyeLiza U Ljungberg
Aug 25, 2021·Phytotherapy Research : PTR·Tingting XiaChanggang Sun

❮ Previous
Next ❯

Methods Mentioned

BETA
Assay
flow cytometry
Protein Assay
PCR
proximity extension assay
electrophoresis

Software Mentioned

ImageJ1
Angiogenesis - Analyzer
Image Studio
QuantStudio 7
GraphPad Prism
Molecular Activity Predictor ( MAP )
Kaluza
Grow
Ingenuity Pathway Analysis
GraphPad

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.