Combined treatment with hyaluronan inhibitor Pep-1 and a selective adenosine A2 receptor agonist reduces inflammation in experimental arthritis
| Autor: | Domenico Puzzolo, Antonio Micali, Angela Avenoso, Salvatore Campo, Antonina Pisani, Angela D'Ascola, Giancarlo Nastasi, Giuseppe M. Campo, Alberto Calatroni, Vera Prestipino, Michele Scuruchi |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Male
Adenosine Nitric Oxide Synthase Type II Arthritis Arthritis Rheumatoid Mice Hyaluronic Acid Receptor hyaluronan arthritis inflammation Cells Cultured Chemistry Adenosine A2 Receptor Antagonists Hyaluronan Receptors Infectious Diseases Mice Inbred DBA Models Animal Cytokines Inflammation Mediators medicine.symptom medicine.drug Agonist medicine.medical_specialty medicine.drug_class Immunology Inflammation Receptor Adenosine A2B Microbiology Internal medicine Matrix Metalloproteinase 13 medicine Animals Humans Synovial fluid Molecular Biology Cell Biology medicine.disease Adenosine A3 receptor Arthritis Experimental Toll-Like Receptor 2 Toll-Like Receptor 4 Endocrinology Gene Expression Regulation Proteolysis TLR4 Joints Peptides |
| Popis: | Investigations have suggested degradation of native hyaluronan (HA) into small oligosaccharides as being involved in the development and progression of inflammatory diseases, particularly rheumatoid arthritis (RA). Inflammatory responses occur by modulating the TLR4 and 2, and the CD44 natural HA receptor. As reported recently, the adenosine A2 receptor (A2AR) plays an important anti-inflammatory role in arthritis. TLR4, TLR2 and CD44 stimulation activate NF-κB, which stimulates the production of pro-inflammatory cytokines and other mediators. In contrast, A2AR stimulation inhibits NF-κB activation. The aim of this study was to investigate the effect of combined treatment of HA inhibitor Pep-1 and a selective A2AR agonist (CV-1808) in collagen-induced arthritis (CIA) in mice. Arthritis was induced via intradermal injection of bovine collagen-II. Mice were treated with Pep-1 plus CV-1808 intraperitoneally daily for 20 d. CIA increased TLR4, TLR2, CD44 and A2AR mRNA expression and the related proteins in the joint cartilage of arthritic mice, where significantly increased concentrations were of TNF-α, IL-1-β, IL-17, matrix metalloprotease-13 and inducible nitric oxide synthase. Pep-1 with CV-1808 treatment significantly reduced CIA damage and all the up-regulated biochemical parameters. These reductions were supported by microscopic analysis and synovial fluid HA levels. |
| Databáze: | OpenAIRE |
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