High mobility group box chromosomal protein 1, a DNA binding cytokine, induces arthritis

Wiley - Tập 48 Số 6 - Trang 1693-1700 - 2003
Rille Pullerits1, Ing‐Marie Jonsson1, Margareta Verdrengh1, Maria Bokarewa1, Jan Andersson2, Helena Erlandsson-Harris3, Andrej Tarkowski1
1Sahlgrenska University Hospital, University of Göteborg, Gothenburg, Sweden
2Astrid Lindgren's Children's Hospital and Rheumatology Research Unit, Karolinska Hospital, Stockholm, Sweden
3Rheumatology research unit, Karolinska Hospital, Stockholm, Sweden

Tóm tắt

AbstractObjectiveTo examine the potential role of high mobility group box chromosomal protein 1 (HMGB‐1) in the pathogenesis of arthritis.MethodsMice were injected intraarticularly with 1 μg or 5 μg of HMGB‐1. Joints were dissected on days 4, 7, and 28 after injection and were evaluated histopathologically and immunohistochemically. To investigate the importance of different white blood cell populations for the development of arthritis, in vivo cell depletion procedures were performed. In addition, spleen cells were cultured in the presence of HMGB‐1, and nuclear factor κB (NF‐κB) activation was detected by electrophoretic mobility shift assay.ResultsInjection of recombinant HMGB‐1 (rHMGB‐1) into different mouse strains resulted in an overall frequency of arthritis in 80% of the animals. The inflammation was characterized by mild to moderate synovitis and lasted for at least 28 days. The majority of cells found in the inflamed synovium were Mac‐1+ macrophages, whereas only a few CD4+ lymphocytes were detected. Pannus formation was observed in some cases 7 and 28 days after HMGB‐1 injection. No significant differences were found with respect to incidence and severity of arthritis between mice depleted of monocytes, granulocytes, or lacking T/B lymphocytes. However, combined removal of monocytes and neutrophils resulted in a 43% lower incidence of arthritis. Mice rendered deficient in the interleukin‐1 (IL‐1) receptor did not develop inflammation upon challenge with HMGB‐1. In vitro data corroborate this finding, showing that rHMGB‐1 activated NF‐κB, a major pathway leading to IL‐1 production.ConclusionOur results indicate that HMGB‐1 is not a mere expression of inflammatory responses, but on its own, it triggers joint inflammation by activating macrophages and inducing production of IL‐1 via NF‐κB activation.

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Tài liệu tham khảo

10.1093/nar/15.21.9077

10.1016/S0021-9258(19)61977-0

10.1093/nar/17.3.1197

10.1128/MCB.19.8.5237

10.1016/S0039-128X(99)00036-7

10.1128/MCB.18.8.4471

10.1038/35012626

10.1242/jcs.113.4.611

10.1126/science.285.5425.248

10.4049/jimmunol.165.6.2950

10.1002/art.10540

10.1084/jem.192.4.565

10.1128/IAI.65.7.2517-2521.1997

10.1002/1529-0131(200010)43:10<2276::AID-ANR15>3.0.CO;2-C

10.1007/BF00918959

10.1002/1529-0131(200002)43:2<356::AID-ANR15>3.0.CO;2-J

10.1016/0022-1759(86)90058-X

10.1002/eji.1830090410

Pierres A, 1984, A rat anti‐mouse T4 monoclonal antibody (H129.19) inhibits the proliferation of Ia‐reactive T cell clones and delineates two phenotypically distinct (T4+, Lyt‐2,3‐, and T4‐, Lyt‐2,3+) subsets among anti‐Ia cytolytic T cell clones, J Immunol, 132, 2775, 10.4049/jimmunol.132.6.2775

10.1111/j.1749-6632.2000.tb05394.x

10.1189/jlb.72.6.1084

Abbas AK, 2000, Cellular and molecular immunology

Van den Berg WB, 1999, TNFα and IL‐1β are separate targets in chronic arthritis, Clin Exp Rheumatol, 17, S105

10.1074/jbc.270.43.25752

Brett J, 1993, Survey of the distribution of a newly characterized receptor for advanced glycation end products in tissues, Am J Pathol, 143, 1699

10.1182/blood-2002-05-1300

10.1074/jbc.274.28.19919

10.1083/jcb.137.1.19

10.1083/jcb.152.6.1197

10.1093/emboj/20.16.4337

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Wiley

Tập 48 Số 6

1693-1700

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