Abstract
Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation and proliferation of synovial membrane tissue. A number of studies have reported the etiologic role of stress proteins in RA. However, the role of the well-characterized stress protein, heme oxygenase-1 (HO-1), in relation to RA, remains to be elucidated. In this investigation, we employed double immunohistochemical staining techniques to identify HO-1-expressing cells in the synovial tissue of a mouse model of RA. The RA model used was that of human T cell leukemia virus type-I (HTLV-I) transgenic (Tg) mouse. The physical characteristics of synovial tissue in limb joints were additionally analyzed. Morphological data revealed a marked increase in the thickness of synovial membrane layers in two- to three month-old Tg mice. HO-1-like immunopositive cells were identified in synovial tissue from both wild-type and HTLV-I Tg mice. Notably, cell numbers in Tg mice were dramatically increased. A double immunofluorescence study revealed the presence of HO-1-immunopositive cells in T cells, fibroblasts and macrophages. The percentage of T cells expressing HO-1 was relatively higher than that of fibroblasts and macrophages. These results suggest that HO-1 levels increase in synovial tissue during RA. Moreover, the protein participates in the regulation of RA pathogenesis.
