↓ Skip to main content

Differential effects of Th1 versus Th2 cytokines in combination with hypoxia on HIFs and angiogenesis in RA

Overview of attention for article published in Arthritis Research & Therapy, August 2012
Altmetric Badge

About this Attention Score

  • Average Attention Score compared to outputs of the same age
  • Average Attention Score compared to outputs of the same age and source

Mentioned by

twitter
4 X users

Citations

dimensions_citation
41 Dimensions

Readers on

mendeley
41 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Differential effects of Th1 versus Th2 cytokines in combination with hypoxia on HIFs and angiogenesis in RA
Published in
Arthritis Research & Therapy, August 2012
DOI 10.1186/ar3934
Pubmed ID
Authors

Helene Larsen, Barbara Muz, Tak L Khong, Marc Feldmann, Ewa M Paleolog

Abstract

ABSTRACT: INTRODUCTION: Hypoxia and T-helper cell 1 (Th1) cytokine-driven inflammation are key features of rheumatoid arthritis (RA) and contribute to disease pathogenesis by promoting angiogenesis. The objective of our study was to characterise the angiogenic gene signature of RA fibroblast-like synoviocytes (FLS) in response to hypoxia, as well as Th1 and T-helper cell 2 (Th2) cytokines, and in particular to dissect out effects of combined hypoxia and cytokines on hypoxia inducible transcription factors (HIFs) and angiogenesis. METHODS: Human angiogenesis PCR arrays were used to screen cDNA from RA FLS exposed to hypoxia (1% oxygen) or dimethyloxalylglycine, which stabilises HIFs. The involvement of HIF isoforms in generating the angiogenic signature of RA FLS stimulated with hypoxia and/or cytokines was investigated using a DNA-binding assay and RNA interference. The angiogenic potential of conditioned media from hypoxia-treated and/or cytokine-treated RA FLS was measured using an in vitro endothelial-based assay. RESULTS: Expression of 12 angiogenic genes was significantly altered in RA FLS exposed to hypoxia, and seven of these were changed by dimethyloxalylglycine, including ephrin A3 (EFNA3), vascular endothelial growth factor (VEGF), adipokines angiopoietin-like (ANGPTL)-4 and leptin. These four proangiogenic genes were dependent on HIF-1 in hypoxia to various degrees: EFNA3 >ANGPTL-4 >VEGF >leptin. The Th1 cytokines TNFα and IL-1β induced HIF-1 but not HIF-2 transcription as well as activity, and this effect was additive with hypoxia. In contrast, Th2 cytokines had no effect on HIFs. IL-1β synergised with hypoxia to upregulate EFNA3 and VEGF in a HIF-1-dependent fashion but, despite strongly inducing HIF-1, TNFα suppressed adipokine expression and had minimal effect on EFNA3. Supernatants from RA FLS subjected to hypoxia and TNFα induced fewer endothelial tubules than those from FLS subjected to TNFα or hypoxia alone, despite high VEGF protein levels. The Th2 cytokine IL-4 strongly induced ANGPTL-4 and angiogenesis by normoxic FLS and synergised with hypoxia to induce further proangiogenic activity. CONCLUSION: The present work demonstrates that Th1 cytokines in combination with hypoxia are not sufficient to induce angiogenic activity by RA FLS despite HIF-1 activation and VEGF production. In contrast, Th2 cytokines induce angiogenic activity in normoxia and hypoxia, despite their inability to activate HIFs, highlighting the complex relationships between hypoxia, angiogenesis and inflammation in RA.

X Demographics

X Demographics

The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 41 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 2%
Spain 1 2%
Germany 1 2%
Unknown 38 93%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 9 22%
Researcher 6 15%
Student > Master 6 15%
Other 4 10%
Student > Bachelor 3 7%
Other 7 17%
Unknown 6 15%
Readers by discipline Count As %
Agricultural and Biological Sciences 13 32%
Medicine and Dentistry 10 24%
Biochemistry, Genetics and Molecular Biology 6 15%
Immunology and Microbiology 5 12%
Veterinary Science and Veterinary Medicine 1 2%
Other 1 2%
Unknown 5 12%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 September 2012.
All research outputs
#14,914,476
of 25,373,627 outputs
Outputs from Arthritis Research & Therapy
#2,162
of 3,381 outputs
Outputs of similar age
#105,518
of 182,990 outputs
Outputs of similar age from Arthritis Research & Therapy
#25
of 40 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. This one is in the 40th percentile – i.e., 40% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,381 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.2. This one is in the 35th percentile – i.e., 35% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 182,990 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 40 others from the same source and published within six weeks on either side of this one. This one is in the 35th percentile – i.e., 35% of its contemporaries scored the same or lower than it.