scholarly journals The Many Faces of Interleukin-6: The Role of IL-6 in Inflammation, Vasculopathy, and Fibrosis in Systemic Sclerosis

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Theresa C. Barnes ◽  
Marina E. Anderson ◽  
Robert J. Moots

Interleukin-6 is currently attracting significant interest as a potential therapeutic target in systemic sclerosis (SSc). In this paper, the biology of interleukin-6 is reviewed, and the evidence for interleukin-6 dysregulation in SSc is explored. The role of inteleukin-6 classical and trans signalling pathways in SSc relevant phenomena such as chronic inflammation, autoimmunity, endothelial cell dysfunction, and fibrogenesis is discussed. The existing evidence that interventions designed to block interleukin-6 signalling are of therapeutic relevance in SSc is evaluated.

1995 ◽  
Vol 117 (2) ◽  
pp. 179-188 ◽  
Author(s):  
Michal Toborek ◽  
Steven W. Barger ◽  
Mark P. Mattson ◽  
Craig J. McClain ◽  
Bernhard Hennig

2014 ◽  
Vol 21 (1) ◽  
pp. 26-37 ◽  
Author(s):  
Enrique Guzmán-Gutiérrez ◽  
Pablo Arroyo ◽  
Rocío Salsoso ◽  
Bárbara Fuenzalida ◽  
Tamara Sáez ◽  
...  

Shock ◽  
2019 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Antony Leonard ◽  
Pei Yi Su ◽  
David I. Yule ◽  
Arshad Rahman ◽  
Fabeha Fazal

2016 ◽  
Vol 6 (2) ◽  
pp. 130-133 ◽  
Author(s):  
Sebastian R. Hobson ◽  
Rutu Acharya ◽  
Rebecca Lim ◽  
Siow Teng Chan ◽  
Joanne Mockler ◽  
...  

Author(s):  
Sebastian R. Hobson ◽  
Rebecca Lim ◽  
Joanne C. Mockler ◽  
Seshini Gurusinghe ◽  
Euan M. Wallace

2018 ◽  
Vol 77 (11) ◽  
pp. 1665-1674 ◽  
Author(s):  
Eloisa Romano ◽  
Mirko Manetti ◽  
Irene Rosa ◽  
Bianca Saveria Fioretto ◽  
Lidia Ibba-Manneschi ◽  
...  

ObjectiveIn systemic sclerosis (SSc), early microvascular injury is followed by impaired angiogenesis and peripheral capillary loss. Here, we investigated the possible contribution of the neurovascular guidance molecule Slit2 and its Roundabout (Robo) receptors to SSc-related endothelial cell dysfunction.MethodsCirculating Slit2 levels were measured in patients with SSc and healthy controls. Slit2, Robo1 and Robo4 expression was investigated in SSc and healthy skin biopsies and explanted dermal microvascular endothelial cells (MVECs). Slit2/Robo4 function in MVEC angiogenesis was studied by cell viability, wound healing and capillary-like tube formation assays.ResultsCirculating Slit2 was significantly increased in either SSc or patients with a very early diagnosis of SSc (VEDOSS) compared with controls. Interestingly, serum Slit2 levels were raised in patients with VEDOSS with nailfold videocapillaroscopy (NVC) abnormalities, while they were similar in VEDOSS with normal NVC and controls. In SSc, Slit2 and Robo4 expression was upregulated in clinically affected skin and explanted MVECs in respect to controls. The angiogenic performance of healthy MVECs was significantly reduced after challenge with recombinant human Slit2 or SSc sera. These inhibitory effects were significantly attenuated when SSc sera were preincubated with an anti-Slit2 blocking antibody. In vitro angiogenesis was severely compromised in SSc-MVECs and could be significantly ameliorated by Slit2 neutralisation or ROBO4 gene silencing. Slit2/Robo4 axis interfered with angiogenesis through the inhibition of Src kinase phosphorylation.ConclusionsIn SSc, increased circulating levels of Slit2 and activation of the Slit2/Robo4 antiangiogenic axis may contribute to peripheral microangiopathy since the very early phase of the disease.


2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Ayako Makino ◽  
Oleksandr Platoshyn ◽  
Jorge Suarez ◽  
Jason X.‐J. Yuan ◽  
Wolfgang H. Dillmann

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