Amelioration of alphavirus-induced arthritis and myositis in a mouse model by treatment with bindarit, an inhibitor of monocyte chemotactic proteins
Autor(es): Rulli Nestor E, Guglielmotti Angelo, Mangano Giorgina, Rolph Michael S, Apicella Claudia, Zaid Ali, Suhrbier Adreas, Mahalingam Suresh
Resumo: Alphaviruses such as chikungunya virus, Sindbis virus, o'nyong-nyong virus, Mayaro virus, - Ross River virus (RRV), are commonly associated with arthralgias - overt arthritides worldwide. Underst-ing the processes by which arthritogenic viruses cause disease is a prerequisite in the quest for better treatments. In this regard, we have recently established that monocyte/macrophages are mediators of alphavirus-induced arthritis in mice. We hypothesized that chemokines associated with monocyte/macrophage recruitment may play an important role in disease. The aim of the present investigations was to determine whether bindarit, an inhibitor of monocyte chemotactic protein (MCP) synthesis, could ameliorate alphavirus-induced rheumatic disease in mice. Using our recently developed mouse model of RRV-induced arthritis, which has many characteristics of RRV disease (RRVD) in humans, the effects of bindarit treatment on RRVD in mice were determined via histologic analyses, immunohistochemistry, flow cytometry, real-time polymerase chain reaction analysis, enzyme-linked immunosorbent assay, - electrophoretic mobility shift assay. Bindarit-treated RRV-infected mice developed mild disease - had substantially reduced tissue destruction - inflammatory cell recruitment as compared with untreated RRV-infected mice. The virus load in the tissues was not affected by bindarit treatment. Bindarit exhibited its activity by down-regulating MCPs, which in turn led to inhibition of cell infiltration - lower production of NF-kappaB - tumor necrosis factor alpha, which are involved in mediating tissue damage. Our data support the use of inhibitors of MCP production in the treatment of arthritogenic alphavirus syndromes - suggest that bindarit may be useful in treating RRVD - other alphavirus-induced arthritides in humans.
Imprenta: Arthritis and Rheumatism, v. 60, n. 8, p. 2513-2523, 2009
Identificador do objeto digital: 10.1002/art.24682
Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Protein synthesis ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya virus - Cytokines ; Chikungunya virus - Viral infections ; Chikungunya virus - Real Time PCR ; Chikungunya Virus - Virus ; Chikungunya virus - Immunology
Data de publicação: 2009
