Amelioration of alphavirus-induced arthritis and myositis in a mouse model by treatment with Bindarit, an inhibitor of monocyte chemotactic proteins

Nestor Rulli, Angelo Guglielmotti, Giorgina Mangano, Michael Rolph, Claudia Apicella, Ali Zaid, Andreas Suhrbier, Suresh Mahalingam

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Alphaviruses such as chikungunya virus, Sindbis virus, o'nyong-nyong virus, Mayaro virus, and Ross River virus (RRV), are commonly associated with arthralgias and overt arthritides worldwide. Understanding 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.

METHODS:
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, and electrophoretic mobility shift assay.

RESULTS:
Bindarit-treated RRV-infected mice developed mild disease and had substantially reduced tissue destruction and 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 and lower production of NF-kappaB and tumor necrosis factor alpha, which are involved in mediating tissue damage.

CONCLUSION:
Our data support the use of inhibitors of MCP production in the treatment of arthritogenic alphavirus syndromes and suggest that bindarit may be useful in treating RRVD and other alphavirus-induced arthritides in humans
Original languageEnglish
Pages (from-to)2513-2523
Number of pages11
JournalArthritis Rheumatism
Volume60
Issue number8
DOIs
Publication statusPublished - 2009

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Monocyte Chemoattractant Proteins
Alphavirus
Ross River virus
Myositis
Arthritis
Virus Diseases
Viruses
Monocytes
Therapeutics
Macrophages
Chikungunya virus
Sindbis Virus
NF-kappa B
Arthralgia
Electrophoretic Mobility Shift Assay
Rheumatic Diseases
Chemokines
bindarit
Real-Time Polymerase Chain Reaction
Flow Cytometry

Cite this

Rulli, Nestor ; Guglielmotti, Angelo ; Mangano, Giorgina ; Rolph, Michael ; Apicella, Claudia ; Zaid, Ali ; Suhrbier, Andreas ; Mahalingam, Suresh. / Amelioration of alphavirus-induced arthritis and myositis in a mouse model by treatment with Bindarit, an inhibitor of monocyte chemotactic proteins. In: Arthritis Rheumatism. 2009 ; Vol. 60, No. 8. pp. 2513-2523.
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title = "Amelioration of alphavirus-induced arthritis and myositis in a mouse model by treatment with Bindarit, an inhibitor of monocyte chemotactic proteins",
abstract = "Alphaviruses such as chikungunya virus, Sindbis virus, o'nyong-nyong virus, Mayaro virus, and Ross River virus (RRV), are commonly associated with arthralgias and overt arthritides worldwide. Understanding 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.METHODS: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, and electrophoretic mobility shift assay.RESULTS:Bindarit-treated RRV-infected mice developed mild disease and had substantially reduced tissue destruction and 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 and lower production of NF-kappaB and tumor necrosis factor alpha, which are involved in mediating tissue damage.CONCLUSION:Our data support the use of inhibitors of MCP production in the treatment of arthritogenic alphavirus syndromes and suggest that bindarit may be useful in treating RRVD and other alphavirus-induced arthritides in humans",
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Rulli, N, Guglielmotti, A, Mangano, G, Rolph, M, Apicella, C, Zaid, A, Suhrbier, A & Mahalingam, S 2009, 'Amelioration of alphavirus-induced arthritis and myositis in a mouse model by treatment with Bindarit, an inhibitor of monocyte chemotactic proteins', Arthritis Rheumatism, vol. 60, no. 8, pp. 2513-2523. https://doi.org/10.1002/art.24682

Amelioration of alphavirus-induced arthritis and myositis in a mouse model by treatment with Bindarit, an inhibitor of monocyte chemotactic proteins. / Rulli, Nestor; Guglielmotti, Angelo; Mangano, Giorgina; Rolph, Michael; Apicella, Claudia; Zaid, Ali; Suhrbier, Andreas; Mahalingam, Suresh.

In: Arthritis Rheumatism, Vol. 60, No. 8, 2009, p. 2513-2523.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Amelioration of alphavirus-induced arthritis and myositis in a mouse model by treatment with Bindarit, an inhibitor of monocyte chemotactic proteins

AU - Rulli, Nestor

AU - Guglielmotti, Angelo

AU - Mangano, Giorgina

AU - Rolph, Michael

AU - Apicella, Claudia

AU - Zaid, Ali

AU - Suhrbier, Andreas

AU - Mahalingam, Suresh

PY - 2009

Y1 - 2009

N2 - Alphaviruses such as chikungunya virus, Sindbis virus, o'nyong-nyong virus, Mayaro virus, and Ross River virus (RRV), are commonly associated with arthralgias and overt arthritides worldwide. Understanding 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.METHODS: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, and electrophoretic mobility shift assay.RESULTS:Bindarit-treated RRV-infected mice developed mild disease and had substantially reduced tissue destruction and 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 and lower production of NF-kappaB and tumor necrosis factor alpha, which are involved in mediating tissue damage.CONCLUSION:Our data support the use of inhibitors of MCP production in the treatment of arthritogenic alphavirus syndromes and suggest that bindarit may be useful in treating RRVD and other alphavirus-induced arthritides in humans

AB - Alphaviruses such as chikungunya virus, Sindbis virus, o'nyong-nyong virus, Mayaro virus, and Ross River virus (RRV), are commonly associated with arthralgias and overt arthritides worldwide. Understanding 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.METHODS: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, and electrophoretic mobility shift assay.RESULTS:Bindarit-treated RRV-infected mice developed mild disease and had substantially reduced tissue destruction and 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 and lower production of NF-kappaB and tumor necrosis factor alpha, which are involved in mediating tissue damage.CONCLUSION:Our data support the use of inhibitors of MCP production in the treatment of arthritogenic alphavirus syndromes and suggest that bindarit may be useful in treating RRVD and other alphavirus-induced arthritides in humans

U2 - 10.1002/art.24682

DO - 10.1002/art.24682

M3 - Article

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EP - 2523

JO - Arthritis Rheumatism

JF - Arthritis Rheumatism

SN - 0004-3591

IS - 8

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