INTRODUCTION: High-mobility group box 1 (HMGB1) has been implicated in angiogenesis and rheumatoid arthritis (RA). The aim of this study was to better define the role of HMGB1 in the synovial angiogenesis and pathogenesis of an immune model of arthritis. METHODS: Balb/c mice were injected with monoclonal anti-collagen antibody cocktail followed by lipopolysaccharide to induce arthritis. RESULTS: HMGB1 and VEGF were over-expressed in the areas of the synovium where more inflammation and neoangiogenesis were present. The selective blockade of HMGB1 or of VEGF alternatively resulted in a lower severity of arthritis evaluated by the arthritis index. Furthermore, exogenous HMGB1 administration caused a worsening of arthritis, associated with VEGF up-regulation and increased synovial angiogenesis. The selective inhibition of VEGF resulted in no induction of arthritis also in mice receiving exogenous HMGB1. Cytokine ELISA analyses performed on peripheral blood and synovial fluid demonstrated a significant reduction of IL-1β , IL-6 and TNF-α in mice where HMGB1 and VEGF pathways were blocked. Interestingly, the selective blockade of HMGB1 and VEGF resulted in an increase of the peripheral IL-17A concentration. CONCLUSIONS: The development of arthritis mediated by HMGB1 and the synovial angiogenesis can be blocked by inhibiting the VEGF activity. The pro-inflammatory and pro-angiogenic cytokine IL-17A is increased when HMGB1 is inhibited, but the synovial angiogenesis is nevertheless reduced in this model of arthritis. Taken together, these findings shed new light on the role of this nuclear protein in the pathogenesis of arthritis in an RA-like model. This article is protected by copyright. All rights reserved.

Biscetti, F., Flex, A., Pecorini, G., Angelini, F., Arena, V., Stigliano, E., Gremese, E., Tolusso, B., Ferraccioli, G., The role of High-mobility group box protein 1 in collagen antibody-induced arthritis is dependent on Vascular endothelial growth factor., <<CLINICAL AND EXPERIMENTAL IMMUNOLOGY>>, 2015; 2016 (Gennaio): 62-72. [doi:10.1111/cei.12758] [http://hdl.handle.net/10807/70511]

The role of High-mobility group box protein 1 in collagen antibody-induced arthritis is dependent on Vascular endothelial growth factor.

Biscetti, Federico;Flex, Andrea;Pecorini, Giovanni;Angelini, Flavia;Arena, Vincenzo;Stigliano, Egidio;Gremese, Elisa;Tolusso, Barbara;Ferraccioli, Gianfranco
2016

Abstract

INTRODUCTION: High-mobility group box 1 (HMGB1) has been implicated in angiogenesis and rheumatoid arthritis (RA). The aim of this study was to better define the role of HMGB1 in the synovial angiogenesis and pathogenesis of an immune model of arthritis. METHODS: Balb/c mice were injected with monoclonal anti-collagen antibody cocktail followed by lipopolysaccharide to induce arthritis. RESULTS: HMGB1 and VEGF were over-expressed in the areas of the synovium where more inflammation and neoangiogenesis were present. The selective blockade of HMGB1 or of VEGF alternatively resulted in a lower severity of arthritis evaluated by the arthritis index. Furthermore, exogenous HMGB1 administration caused a worsening of arthritis, associated with VEGF up-regulation and increased synovial angiogenesis. The selective inhibition of VEGF resulted in no induction of arthritis also in mice receiving exogenous HMGB1. Cytokine ELISA analyses performed on peripheral blood and synovial fluid demonstrated a significant reduction of IL-1β , IL-6 and TNF-α in mice where HMGB1 and VEGF pathways were blocked. Interestingly, the selective blockade of HMGB1 and VEGF resulted in an increase of the peripheral IL-17A concentration. CONCLUSIONS: The development of arthritis mediated by HMGB1 and the synovial angiogenesis can be blocked by inhibiting the VEGF activity. The pro-inflammatory and pro-angiogenic cytokine IL-17A is increased when HMGB1 is inhibited, but the synovial angiogenesis is nevertheless reduced in this model of arthritis. Taken together, these findings shed new light on the role of this nuclear protein in the pathogenesis of arthritis in an RA-like model. This article is protected by copyright. All rights reserved.
Inglese
Biscetti, F., Flex, A., Pecorini, G., Angelini, F., Arena, V., Stigliano, E., Gremese, E., Tolusso, B., Ferraccioli, G., The role of High-mobility group box protein 1 in collagen antibody-induced arthritis is dependent on Vascular endothelial growth factor., <<CLINICAL AND EXPERIMENTAL IMMUNOLOGY>>, 2015; 2016 (Gennaio): 62-72. [doi:10.1111/cei.12758] [http://hdl.handle.net/10807/70511]
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