IL-17 mediates articular hypernociception in antigen-induced arthritis in mice
| Autor: | Larissa G. Pinto, Waldiceu A. Verri, Silvio M. Vieira, Henrique Lemos, Sergio H. Ferreira, Fernando Q. Cunha, Thiago M. Cunha |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Pain Threshold
medicine.hormone medicine.medical_specialty Neutrophils medicine.drug_class medicine.medical_treatment Arthritis Dinoprostone Endothelins Mice Cell Movement Polysaccharides Internal medicine Animals Medicine Antigens Enzyme Inhibitors Serum Albumin Mice Knockout Analysis of Variance Mice Inbred BALB C business.industry Interleukin-17 Zymosan Antagonist Antibodies Monoclonal Receptor antagonist medicine.disease Infliximab Mice Inbred C57BL Disease Models Animal Anesthesiology and Pain Medicine Cytokine medicine.anatomical_structure Endocrinology Gene Expression Regulation Neurology Eicosanoid Hyperalgesia Receptors Tumor Necrosis Factor Type I Antirheumatic Agents Cytokines Neurology (clinical) Interleukin 17 Synovial membrane business |
| Zdroj: | Pain. 148:247-256 |
| ISSN: | 0304-3959 |
| DOI: | 10.1016/j.pain.2009.11.006 |
| Popis: | IL-17 is an important cytokine in the physiopathology of rheumatoid arthritis (RA). However, its participation in the genesis of nociception during RA remains undetermined. In this study, we evaluated the role of IL-17 in the genesis of articular nociception in a model of antigen (mBSA)-induced arthritis. We found that mBSA challenge in the femur-tibial joint of immunized mice induced a dose- and time-dependent mechanical hypernociception. The local IL-17 concentration within the mBSA-injected joints increased significantly over time. Moreover, co-treatment of mBSA challenged mice with an antibody against IL-17 inhibited hypernociception and neutrophil recruitment. In agreement, intraarticular injection of IL-17 induced hypernociception and neutrophil migration, which were reduced by the pre-treatment with fucoidin, a leukocyte adhesion inhibitor. The hypernociceptive effect of IL-17 was also reduced in TNFR1(-/-) mice and by pre-treatment with infliximab (anti-TNF antibody), a CXCR1/2 antagonist or by an IL-1 receptor antagonist. Consistent with these findings, we found that IL-17 injection into joints increased the production of TNF-alpha, IL-1beta and CXCL1/KC. Treatment with doxycycline (non-specific MMPs inhibitor), bosentan (ET(A)/ET(B) antagonist), indomethacin (COX inhibitor) or guanethidine (sympathetic blocker) inhibited IL-17-induced hypernociception. IL-17 injection also increased PGE(2) production, MMP-9 activity and COX-2, MMP-9 and PPET-1 mRNA expression in synovial membrane. These results suggest that IL-17 is a novel pro-nociceptive cytokine in mBSA-induced arthritis, whose effect depends on both neutrophil migration and various pro-inflammatory mediators, as TNF-alpha, IL-1beta, CXCR1/2 chemokines ligands, MMPs, endothelins, prostaglandins and sympathetic amines. Therefore, it is reasonable to propose IL-17 targeting therapies to control this important RA symptom. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|