Smac127 Has Proapoptotic and Anti-Inflammatory Effects on Rheumatoid Arthritis Fibroblast-Like Synoviocytes
Joint Authors
Ingegnoli, Francesca
Gualtierotti, Roberta
Casnici, Claudia
Lattuada, Donatella
Crotta, Katia
Corradini, Costantino
Marelli, Ornella
Seneci, P.
Viganò, R.
Source
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-9, 9 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-02-17
Country of Publication
Egypt
No. of Pages
9
Main Subjects
Abstract EN
Rheumatoid arthritis (RA) is characterized by synovial inflammation and hyperplasia.
Fibroblast-like synoviocytes (FLSs) are apoptosis-resistant and contribute to the pathogenesis of RA by producing cytokines and proteolytic enzymes, which degrade the extracellular matrix.
We evaluated the proapoptotic and anti-inflammatory activity of the small molecule Smac127 on RA-FLSs cultured in synovial fluid (SF), in order to reproduce the physiopathological environmental characteristic of RA joints.
In this context, Smac127 induces apoptosis by inhibiting apoptosis proteins (IAPs).
This inhibition activates caspase 3 and restores the apoptotic pathway.
In addition, Smac127 induces a significant inhibition of the secretion of IL-15 and IL-6, stimulation of pannus formation, and damage of bone and cartilage in RA.
Also the secretion of the anti-inflammatory cytokine IL-10 is dramatically increased in the presence of Smac127.
The cartilage destruction in RA patients is partly mediated by metalloproteinases; here we show that the MMP-1 production by fibroblasts cultured in SF is significantly antagonized by Smac127.
Conversely, this molecule has no significant effects on RANKL and OPG production.
Our observations demonstrate that Smac127 has beneficial regulatory effects on inflammatory state of RA-FLSs and suggest a potential use of Smac127 for the control of inflammation and disease progression in RA.
American Psychological Association (APA)
Lattuada, Donatella& Gualtierotti, Roberta& Crotta, Katia& Seneci, P.& Ingegnoli, Francesca& Corradini, Costantino…[et al.]. 2016. Smac127 Has Proapoptotic and Anti-Inflammatory Effects on Rheumatoid Arthritis Fibroblast-Like Synoviocytes. Mediators of Inflammation،Vol. 2016, no. 2016, pp.1-9.
https://search.emarefa.net/detail/BIM-1111173
Modern Language Association (MLA)
Lattuada, Donatella…[et al.]. Smac127 Has Proapoptotic and Anti-Inflammatory Effects on Rheumatoid Arthritis Fibroblast-Like Synoviocytes. Mediators of Inflammation No. 2016 (2016), pp.1-9.
https://search.emarefa.net/detail/BIM-1111173
American Medical Association (AMA)
Lattuada, Donatella& Gualtierotti, Roberta& Crotta, Katia& Seneci, P.& Ingegnoli, Francesca& Corradini, Costantino…[et al.]. Smac127 Has Proapoptotic and Anti-Inflammatory Effects on Rheumatoid Arthritis Fibroblast-Like Synoviocytes. Mediators of Inflammation. 2016. Vol. 2016, no. 2016, pp.1-9.
https://search.emarefa.net/detail/BIM-1111173
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1111173