Objectives: Human six-transmembrane epithelial antigen of prostate 4 (STEAP4) is one of the STEAP family as a homologue of mouse tumour necrosis factor-α-induced adipose-related protein (TIARP). Recently, we reported that the TIARP gene expression was remarkably increased in spleen and joints of glucose-6-phosphate isomerise (GPI)-induced arthritis model, suggesting pivotal association to arthritis. The aim of the present study was to assess the expression, localisation and function of STEAP4 in peripheral blood of patients with rheumatoid arthritis (RA).
Methods: Peripheral blood was obtained from seven patients with RA, the surface expression of STEAP4 was detected by flow cytometry. The number of neutrophils was compared with the expression of STEAP4 mRNA derived from peripheral blood of patients with RA. Neutrophils were introduced by HL60 with retinoic acid, and were transfected with GFP-STEAP4 plasmid DNA, then the migration of neutrophil-like HL60 was determined by transwell assay. In addition, the fluctuation of STEAP4 mRNA was analysed before and after treatment with infliximab in 40 patients with RA.
Results: STEAP4 was expressed on monocytes and neutrophils in peripheral blood in RA. The number of neutrophils and expression of STEAP4 mRNA was positively correlated. Migration of neutrophil-like HL60 was down-regulated by over-expression of STEAP4. Expression of STEAP4 Mrna was significantly decreased after infliximab treatment in patients with RA, especially in good responders.
Conclusions: STEAP4 is expressed on monocytes and neutrophils in peripheral blood, regulates cell migration, is down-regulated by TNF antagonist, and might be a possible predictor of response to TNF antagonist.