high mobility group box 1 potentiates the pro-inflammatory effects of interleukin-1β in osteoarthritic synoviocytes高机动组框1强化interleukin-1β的促炎作用在骨关节炎synoviocytes.pdfVIP

high mobility group box 1 potentiates the pro-inflammatory effects of interleukin-1β in osteoarthritic synoviocytes高机动组框1强化interleukin-1β的促炎作用在骨关节炎synoviocytes.pdf

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García-Arnandis et al. Arthritis Research Therapy 2010, 12:R165 /content/12/4/R165 RESEARCH ARTICLE Open Access High mobility group box 1 potentiates the pro-inflammatory effects of interleukin-1b in osteoarthritic synoviocytes 1 1,2 3 4 4 Isabel García-Arnandis , Maria Isabel Guillén , Francisco Gomar , Jean-Pierre Pelletier , Johanne Martel-Pelletier , Maria José Alcaraz1* Abstract Introduction: High mobility group box 1 (HMGB1) is released by necrotic cells or secreted in response to inflammatory stimuli. Extracellular HMGB1 may act as a pro-inflammatory cytokine in rheumatoid arthritis. We have recently reported that HMGB1 is released by osteoarthritic synoviocytes after activation with interleukin-1beta (IL- 1b) The present study investigated the role of HMGB1 in synovial inflammation in osteoarthritis (OA). Methods: HMGB1 was determined in human synovium using immunohistochemistry, comparing normal to OA. OA synoviocytes were incubated with HMGB1 at 15 or 25 ng/ml in the absence or presence of IL-1b (10 ng/ml). Gene expression was analyzed by quantitative PCR and protein expression by Western Blot and ELISA. Matrix metalloproteinase (MMP) activity was studied by fluorometric procedures and nuclear factor (NF)-B activation by transient transfection with a NF-B-luciferase plasmid. Results: In the normal synovium, HMGB1 was found in the synovial lining cells, sublining cells, and in the vascular wall cells. The distribution of HMGB1 in OA synovium was similar but the number of HMGB1 positive cells was higher and HMGB1 was also present in infiltrated cells. In normal synovial membrane cells, HMGB1 was found mostly in the nuclei, whereas in OA, HMGB1 was generally found mostly

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