An inflammation loop orchestrated by S100A9 and calprotectin is critical for development of arthritis.
The S100A9 and S100A8 proteins are highly expressed by neutrophils and monocytes and are part of a group of damage-associated molecular pattern molecules that trigger inflammatory responses. Sera and synovial fluids of patients with rheumatoid arthritis (RA) contain high concentrations of S100A8/A9...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3445527?pdf=render |
| _version_ | 1818321527478681600 |
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| author | Annabelle Cesaro Nadia Anceriz Audrey Plante Nathalie Pagé Mélanie R Tardif Philippe A Tessier |
| author_facet | Annabelle Cesaro Nadia Anceriz Audrey Plante Nathalie Pagé Mélanie R Tardif Philippe A Tessier |
| author_sort | Annabelle Cesaro |
| collection | DOAJ |
| description | The S100A9 and S100A8 proteins are highly expressed by neutrophils and monocytes and are part of a group of damage-associated molecular pattern molecules that trigger inflammatory responses. Sera and synovial fluids of patients with rheumatoid arthritis (RA) contain high concentrations of S100A8/A9 that correlate with disease activity.In this study, we investigated the importance of S100A9 in RA by using neutralizing antibodies in a murine lipopolysaccharide-synchronized collagen-induced arthritis model. We also used an in vitro model of stimulation of human immune cells to decipher the role played by S100A9 in leukocyte migration and pro-inflammatory cytokine secretion.Treatment with anti-S100A9 antibodies improved the clinical score by 50%, diminished immune cell infiltration, reduced inflammatory cytokines, both in serum and in the joints, and preserved bone/collagen integrity. Stimulation of neutrophils with S100A9 protein led to the enhancement of neutrophil transendothelial migration. S100A9 protein also induced the secretion by monocytes of proinflammatory cytokines like TNFα, IL-1β and IL-6, and of chemokines like MIP-1α and MCP-1.The effects of anti-S100A9 treatment are likely direct consequences of inhibiting the S100A9-mediated promotion of neutrophil transmigration and secretion of pro-inflammatory cytokines from monocytes. Collectively, our results show that treatment with anti-S100A9 may inhibit amplification of the immune response and help preserve tissue integrity. Therefore, S100A9 is a promising potential therapeutic target for inflammatory diseases like rheumatoid arthritis for which alternative therapeutic strategies are needed. |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T10:42:19Z |
| publishDate | 2012-01-01 |
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| series | PLoS ONE |
| spelling | doaj.art-f3591027e0864bb38ebae79d66cada9f2022-12-21T23:50:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0179e4547810.1371/journal.pone.0045478An inflammation loop orchestrated by S100A9 and calprotectin is critical for development of arthritis.Annabelle CesaroNadia AncerizAudrey PlanteNathalie PagéMélanie R TardifPhilippe A TessierThe S100A9 and S100A8 proteins are highly expressed by neutrophils and monocytes and are part of a group of damage-associated molecular pattern molecules that trigger inflammatory responses. Sera and synovial fluids of patients with rheumatoid arthritis (RA) contain high concentrations of S100A8/A9 that correlate with disease activity.In this study, we investigated the importance of S100A9 in RA by using neutralizing antibodies in a murine lipopolysaccharide-synchronized collagen-induced arthritis model. We also used an in vitro model of stimulation of human immune cells to decipher the role played by S100A9 in leukocyte migration and pro-inflammatory cytokine secretion.Treatment with anti-S100A9 antibodies improved the clinical score by 50%, diminished immune cell infiltration, reduced inflammatory cytokines, both in serum and in the joints, and preserved bone/collagen integrity. Stimulation of neutrophils with S100A9 protein led to the enhancement of neutrophil transendothelial migration. S100A9 protein also induced the secretion by monocytes of proinflammatory cytokines like TNFα, IL-1β and IL-6, and of chemokines like MIP-1α and MCP-1.The effects of anti-S100A9 treatment are likely direct consequences of inhibiting the S100A9-mediated promotion of neutrophil transmigration and secretion of pro-inflammatory cytokines from monocytes. Collectively, our results show that treatment with anti-S100A9 may inhibit amplification of the immune response and help preserve tissue integrity. Therefore, S100A9 is a promising potential therapeutic target for inflammatory diseases like rheumatoid arthritis for which alternative therapeutic strategies are needed.http://europepmc.org/articles/PMC3445527?pdf=render |
| spellingShingle | Annabelle Cesaro Nadia Anceriz Audrey Plante Nathalie Pagé Mélanie R Tardif Philippe A Tessier An inflammation loop orchestrated by S100A9 and calprotectin is critical for development of arthritis. PLoS ONE |
| title | An inflammation loop orchestrated by S100A9 and calprotectin is critical for development of arthritis. |
| title_full | An inflammation loop orchestrated by S100A9 and calprotectin is critical for development of arthritis. |
| title_fullStr | An inflammation loop orchestrated by S100A9 and calprotectin is critical for development of arthritis. |
| title_full_unstemmed | An inflammation loop orchestrated by S100A9 and calprotectin is critical for development of arthritis. |
| title_short | An inflammation loop orchestrated by S100A9 and calprotectin is critical for development of arthritis. |
| title_sort | inflammation loop orchestrated by s100a9 and calprotectin is critical for development of arthritis |
| url | http://europepmc.org/articles/PMC3445527?pdf=render |
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