Upregulation of 78-kDa glucose-regulated protein in macrophages in peripheral joints of active ankylosing spondylitis

Objectives: To investigate the expression of the 78-kDa glucose-regulated protein (GRP78), a marker of activation of the unfolded protein response (UPR), in macrophages of ankylosing spondylitis (AS) synovium and synovial fluid and to explore the relationship between the expression of GRP78 and synovial fluid levels of the proinflammatory cytokines, as well as the inflammatory activity of AS. Methods: Immunohistochemical staining and Western blotting were performed to detect the expression of GRP78 in macrophages in the involved peripheral joints of 16 patients with active AS, and in 15 patients with osteoarthritis (OA) as controls. Synovial fluid levels of tumour necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6) of AS peripheral joints were measured using an enzyme-liked immunosorbent assay (ELISA). The inflammatory activity of AS was measured by the sera levels of IL-6 and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Results: Expression of GRP78 in macrophages was increased significantly in the affected peripheral joints of AS compared with OA patients. Positive correlations were found between the expression of GRP78 in macrophages in AS-affected peripheral joints and the synovial fluid levels of TNF alpha and IL-16, as well as the sera levels of IL-6 and the BASDAI. Conclusions: Activation of the UPR occurs in macrophages in both the synovium and synovial fluids of AS-involved peripheral joints, and there may be a link between activation of the UPR of macrophages and local production of the proinflammatory cytokines, as well as the inflammatory activity of AS.