Ankylosing spondylitis macrophage production of higher levels of interleukin‐23 in response to lipopolysaccharide without induction of a significant unfolded protein response

Objective Previous studies of the HLA–B27–transgenic rat model of ankylosing spondylitis (AS) suggested that macrophages develop an intracellular stress response called the unfolded protein response (UPR) and, as a result, secrete increased amounts of cytokines in response to Toll‐like receptor agonists such as lipopolysaccharide (LPS). Our objective was to determine whether macrophages from AS patients also undergo a UPR and secrete increased cytokines/chemokines in response to LPS. Methods Peripheral blood monocytes isolated from 10 AS patients and 10 healthy controls were differentiated in vitro with macrophage colony‐stimulating factor. Select samples were treated with interferon‐γ (IFNγ) to up‐regulate class I major histocompatibility complex (HLA–B) expression prior to stimulation with LPS for either 3 hours (for RNA) or 8–24 hours (for supernatant). UPR induction was assessed by measuring the expression of messenger RNA for ERdj4, BiP, and CCAAT/enhancer binding protein homologous protein 10 (CHOP). Results Although IFNγ treatment up‐regulated HLA–B expression (2‐fold; P < 0.0001), neither IFNγ nor LPS substantially enhanced BiP or CHOP expression (