Use este identificador para citar ou linkar para este item: https://repositorio.inpa.gov.br/handle/1/18351
Título: IL-17 mediates articular hypernociception in antigen-induced arthritis in mice
Autor: Pinto, Larissa Garcia
Cunha, Thiago Mattar
Manfredo Vieira, Silvio
Lemos, Henrique Paula
Verri, Waldiceu A.
Cunha, Fernando Queiroz
Ferreira, Seérgio Henrique
Palavras-chave: Antigen
Bosentan
Cxcl1 Chemokine
Doxycycline
Endothelin
Fucoidin
Gelatinase B
Guanethidine
Indometacin
Infliximab
Interleukin-17
Interleukin-1beta
Prostaglandin E2
Tumor Necrosis Factor-alpha
Animals Experiment
Animals Model
Arthritis
Cell Migration
Controlled Study
Cytokine Production
Drug Inhibition
Enzyme Activity
Male
Mouse
Neutrophil
Nociception
Nonhuman
Pain
Priority Journal
Analysis Of Variance
Animal
Antibodies, Monoclonal
Antigens
Antirheumatic Agents
Arthritis
Cell Movement
Cytokines
Dinoprostone
Disease Models, Animals
Endothelins
Enzyme Inhibitors
Gene Expression Regulation
Hyperalgesia
Interleukin-17
Mice
Mice, Inbred Balb C
Mice, Inbred C57bl
Mice, Knockout
Neutrophils
Pain Threshold
Polysaccharides
Receptors, Tumor Necrosis Factor, Type I
Serum Albumin
Zymosan
Data do documento: 2010
Revista: Pain
É parte de: Volume 148, Número 2, Pags. 247-256
Abstract: 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-α, IL-1β and CXCL1/KC. Treatment with doxycycline (non-specific MMPs inhibitor), bosentan (ETA/ETB antagonist), indomethacin (COX inhibitor) or guanethidine (sympathetic blocker) inhibited IL-17-induced hypernociception. IL-17 injection also increased PGE2 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-α, IL-1β, 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. © 2009 International Association for the Study of Pain.
DOI: 10.1016/j.pain.2009.11.006
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