Giulia Benedetti, Paola Bonaventura, Fabien Lavocat, Pierre Miossec
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory disorder, characterized by a persistent immune cell infiltrate in the synovium accompanied by high levels of inflammatory mediators and synovial hyperplasia. Despite significant therapeutic advances, RA remains an important unmet medical need. To discover potential new genes controlling inflammation and apoptosis in synoviocytes, genes induced by the two pro-inflammatory cytokines, tumor necrosis factor α (TNF-α) and interleukin 17A (IL-17A), were systematically searched. We identified Amphoterin-induced gene and ORF 2 (Amigo-2), a novel antiapoptotic adhesion molecule, as synergistically upregulated by the IL-17A/TNF combination specifically in RA synoviocytes. In addition, when RA synoviocytes were cocultured with immune cells, Amigo2 expression was significantly increased in both fibroblasts and immune cells. This induction persisted in RA synoviocytes even after the removal of the immune cells. Amigo2 induction was ERK-dependent and on the contrary, inhibited by JNK. Furthermore, Amigo2 expression levels correlated with apoptosis of the cells when exposed to the proapoptotic agent cadmium (Cd). Interestingly, exposure of the cells to HMGB1 in inflammatory conditions increased synergistically Amigo2 expression and significantly reduced Cd-mediated cellular toxicity. Our findings support a model whereby cell-cell contact with immune cells and exposure to the combination of both inflammatory cytokines and HMGB1 in the joints of RA patients increases Amigo2 expression in synoviocytes in an ERK-dependent manner which, in turn, enhances cellular adhesion and promotes cell survival and cellular proliferation.
Pharmacology, Toxicology and Pharmaceutical Science
3
14%
Biochemistry, Genetics and Molecular Biology
3
14%
Neuroscience
3
14%
Immunology and Microbiology
3
14%
Medicine and Dentistry
3
14%
Other
3
14%
Unknown
4
18%
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 24 August 2016.
All research outputs
#15,115,571
of 26,184,649 outputs
Outputs from Frontiers in immunology
#12,876
of 33,037 outputs
Outputs of similar age
#195,223
of 370,626 outputs
Outputs of similar age from Frontiers in immunology
#56
of 122 outputs
Altmetric has tracked 26,184,649 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
So far Altmetric has tracked 33,037 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.5. This one has gotten more attention than average, scoring higher than 59% of its peers.
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 370,626 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 46th percentile – i.e., 46% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 122 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.
