Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose:
High mobility group box 1 (HMGB1) is a crucial cytokine that mediated the response to infection, injury and inflammation. It is recently discovered that HMGB1 plays a role in the pathogenesis of inflammatory arthritis, such as rheumatoid arthritis. However, the role of HMGB1 in gouty arthritis has not yet determined. The purpose of the study was to investigate the role HMGB1 in gouty arthritis
Methods: HMGB1 concentrations of the synovial fluid (SF) of gouty arthritis and osteoarthritis (OA) were measured by ELISA. Immunohistochemistry was performed in synovial tissue of gouty arthritis and OA. Double immunofluorescence staining was also performed using anti-CD55, anti-CD68, and anti-HMGB1 antibody. In vitro THP-1 cell was stimulated by monosodium urate (MSU) crystal and lipopolysaccharide (LPS). HMGB1 and IL-1β concentrations were measured by ELISA. THP-1 cell and synovial fibroblast were stimulated by IL-1β alone or in complex with HMGB1. IL-1β, IL-6, TNF-α levels were measured by ELISA, and cyclooxygenase-2 (COX-2) expression was assessed by Western blot.
Results:
HMGB1 concentration was significantly higher in SF of gouty arthritis than that of OA (73.1±57.1 vs 14.8±7.3, p < 0.01). Immunohistochemistry revealed that HMGB1 was localized in the nucleus of synoviocyte in OA. However, in gouty arthritis, HMGB1 was found in the cytoplasm of synoviocyte as well as nucleus. Double immunofluorescence staining showed that HMGB1 was found in mainly synovial fibroblast in gouty arthritis. MSU crystal and LPS induced HMGB1 and IL-1β production in THP-1 cell. However, IL-1β, IL-6, TNF-α levels and COX-2 expression were not stimulated by IL-1β alone or IL-1β/HMGB1 complex in THP-1 cell. IL-1β alone enhance COX-2 expression, but IL-1β/HMGB1 complex decreased COX-2 expression in synovial fibroblast.
Conclusion: HMGB1 was highly expressed in SF and synovial tissue in gouty arthritis. MSU crystal and LPS induced HMGB-1 and IL-1β production in macrophage. Extracellular HMGB1 decreased IL-1β induced COX-2 expression in synovial fibroblast. These findings suggest that HMGB1 might plays as an anti-inflammatory mediator in gouty arthritis.
Disclosure:
K. Moon,
None;
J. Kim,
None;
Y. J. Lee,
None.
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