| Full text | |
| Author(s): |
Veras, Flavio P.
[1]
;
Peres, Raphael S.
[1]
;
Saraiva, Andre L. L.
[1]
;
Pinto, Larissa G.
[1]
;
Louzada-Junior, Paulo
[2, 3]
;
Cunha, Thiago M.
[1, 3]
;
Paschoal, Jonas A. R.
[4]
;
Cunha, Fernando Q.
[1, 3]
;
Alves-Filho, Jose C.
[1, 3]
Total Authors: 9
|
| Affiliation: | [1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, BR-14049 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, BR-14049 Ribeirao Preto, SP - Brazil
[3] Univ Sao Paulo, Ribeirao Preto Med Sch, Ctr Res Inflammatory Dis, BR-14049 Ribeirao Preto, SP - Brazil
[4] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, BR-14049 Ribeirao Preto, SP - Brazil
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | SCIENTIFIC REPORTS; v. 5, OCT 19 2015. |
| Web of Science Citations: | 20 |
| Abstract | |
Fructose 1,6-bisphosphate (FBP) is an endogenous intermediate of the glycolytic pathway. Exogenous administration of FBP has been shown to exert protective effects in a variety of ischemic injury models, which are attributed to its ability to sustain glycolysis and increase ATP production. Here, we demonstrated that a single treatment with FBP markedly attenuated arthritis, assessed by reduction of articular hyperalgesia, joint swelling, neutrophil infiltration and production of inflammatory cytokines, TNF and IL-6, while enhancing IL-10 production in two mouse models of arthritis. Our mechanistic studies showed that FBP reduces joint inflammation through the systemic generation of extracellular adenosine and subsequent activation of adenosine receptor A2a (A2aR). Moreover, we showed that FBP-induced adenosine generation requires hydrolysis of extracellular ATP through the activity of the ectonucleosides triphosphate diphosphohydrolase-1 (ENTPD1, also known as CD39) and ecto-5'-nucleotidase (E5NT, also known as CD73). In accordance, inhibition of CD39 and CD73 abolished anti-arthritic effects of FBP. Taken together, our findings provide a new insight into the molecular mechanism underlying the anti-inflammatory effect of FBP, showing that it effectively attenuates experimental arthritis by activating the anti-inflammatory adenosinergic pathway. Therefore, FBP may represent a new therapeutic strategy for treatment of rheumatoid arthritis (RA). (AU) | |
| FAPESP's process: | 13/08216-2 - CRID - Center for Research in Inflammatory Diseases |
| Grantee: | Fernando de Queiroz Cunha |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |
| FAPESP's process: | 09/54014-7 - Acquisition of a biophotonic imaging system and a multiphoton microscopy system for in vivo imaging |
| Grantee: | Enilza Maria Espreafico |
| Support Opportunities: | Multi-user Equipment Program |
| FAPESP's process: | 11/19670-0 - Mechanisms involved in the pathophysiology of rheumatoid arthritis, pain and sepsis |
| Grantee: | Fernando de Queiroz Cunha |
| Support Opportunities: | Research Projects - Thematic Grants |