Morphological characterization of intra-articular HMGB1 expression during the course of collagen-induced arthritis
| Autor: | Erik Sundberg, Karin Palmblad, Ann-Charlotte Aveberger, Helena Erlandsson Harris, Riikka Söderling, Margarita Diez, Ulf Andersson |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Cytoplasm Pathology medicine.medical_specialty Time Factors medicine.medical_treatment Interleukin-1beta Immunology Type II collagen Fluorescent Antibody Technique Arthritis chemical and pharmacologic phenomena Inflammation In situ hybridization Biology HMGB1 Rheumatology Synovitis medicine Animals Immunology and Allergy RNA Messenger HMGB1 Protein In Situ Hybridization Cell Nucleus Tumor Necrosis Factor-alpha Synovial Membrane High Mobility Group Proteins medicine.disease Arthritis Experimental Immunohistochemistry Rats Repressor Proteins Cytokine biology.protein Tumor necrosis factor alpha Collagen medicine.symptom Research Article |
| Zdroj: | Arthritis Research & Therapy |
| ISSN: | 1478-6354 |
| DOI: | 10.1186/ar2155 |
| Popis: | High-mobility group chromosomal box protein 1 (HMGB1) is a structural nuclear protein that promotes inflammation when present extracellularly. Aberrant, extracellular HMGB1 expression has been demonstrated in human and experimental synovitis. The aim of the present study was to elucidate the temporal and spatial expression of HMGB1 compared to that of the central mediators tumor necrosis factor (TNF) and interleukin-1-beta (IL-1beta) during the course of collagen-induced arthritis. Thus, Dark Agouti rats were immunized with homologous type II collagen and synovial tissue specimens were obtained at various time points prior to and during the course of clinical arthritis. Local cytokine responses were assessed by immunohistochemistry and by in situ hybridization. We demonstrate a distinct nuclear expression of HMGB1 at early disease-preceding time points. Preceding clinical onset by a few days, cytoplasmic HMGB1 expression was evident in synoviocytes within the non-proliferative lining layer. Pronounced cytoplasmic and additional extracellular HMGB1 expression coincided with the progression of clinical disease. In advanced arthritis, the number of cells with cytoplasmic HMGB1 expression was quantitatively comparable to that of cells expressing TNF and IL-1beta. Interestingly, although HMGB1 was abundantly expressed throughout the inflamed synovium at a protein level, upregulation of HMGB1 mRNA was restricted mainly to areas of cartilage and bone destruction. In conclusion, these new findings implicate a role for HMGB1 in both inducing and perpetuating inflammatory events of significant importance in the destructive processes in chronic arthritis. |
| Databáze: | OpenAIRE |
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